Category Archives: Stem Cell Therapy

Adnan F. Danish, MD, chief, Division of Radiation Oncology, St. Josephs Health; radiation oncologist, John Theurer Cancer Center, Hackensack University Medical Center, discusses findings from a study evaluating the prevalence of patients with high-risk non-Hodgkin lymphoma (NHL) who were eligible for bridging radiation therapy prior to receiving CAR T-cell therapy, as well as the outcomes of these patients following CAR T-cell therapy.

This single-center, retrospective study included 81 patients with relapsed/refractory NHL who received CAR T-cell therapy between the years of 2018 and 2022. The CAR T-cell products that patients received included axicabtagene ciloleucel (Yescarta; 62%), lisocabtagene maraleucel (Breyanzi; 16%), tisagenlecleucel (Kymriah; 15%), and brexucabtagene autoleucel (Tecartus; 7%).

Patients were deemed eligible for bridging radiation therapy if they had less than 5 malignant lesions according to pre-apheresis radiological study results. Patients were classified as having high-risk disease if they had bulky disease of at least 10 cm, at least 1 extranodal site, lactate dehydrogenase levels above normal, or at least 1 lesion with an SUVmax of at least 10. Investigators found that 40 patients (49%) included in this study would have been eligible for bridging radiation therapy. Among these patients, 29 had disease with high-risk features, including 4 with bulky disease, 6 with 1 or more lesions with an SUVmax of at least 10, and 2 with at least 1 extranodal site. Of the 40 eligible patients, 9 received bridging radiation therapy, 2 of whom had high-risk disease.

Among patients with a high risk of disease relapse after CAR T-cell therapy, 44% experienced either a partial response, stable disease, or progressive disease at 3 months postCAR T-cell therapy. Moreover, 1 patient with transformed diffuse large B-cell lymphoma (DLBCL) had persistent disease in the nasopharynx following 3 cycles of R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine, and dexamethasone). This patient received radiation therapy as a bridge to CAR T-cell therapy, which led to a continued complete response (CR) at 23 months of follow-up. Another notable patient with nondouble-hit, germinal center Blike DLBCL achieved a CR with 6 cycles of R-CHOP, and experienced disease relapse less than 1 year later. This patient then received bridging radiation therapy, and experienced disease relapse 6 months after CAR T-cell therapy.

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Dr Danish on Post-CAR T-Cell Bridging Radiation Therapy Eligibility ... - OncLive

The proliferation of preoperative neoadjuvant trials with immune-oncology (IO) alone or IO plus chemotherapy has led to a consistent wave of opportunities in locally advanced disease in the upfront setting across many solid tumors. At the European Society for Medical Oncology (ESMO) Congress 2023, Tina Cascone, MD, and colleagues1 presented data from a late-breaking abstract about the benefit of adding the PD-1 inhibitor nivolumab (Opdivo) to chemotherapy for patients with stage II to IIIB nonsmall cell lung cancer or head and neck cancer, as well as other solid tumors. We are seeing a greater application of these neoadjuvant approaches and combinations of IO-IO, IO plus chemotherapy, and sometimes IO with stereotactic radiation, leading to substantial tumor reductions and, in some cases, deep or complete responses.

In the past, the effort to identify biomarkers of response was one of the goals of these trials, whereas now the responses are deep and durable enough to permit alterations in clinical decision-making. Organ preservation and reduced extent of surgical resection are potential dramatic benefits, coupled with the prospect of immune memory, leading to reduction in tumor, recurrence, and subsequently improved overall survival. It appears that inflamed tumors at baseline, as well as those with high expression of the ligand PD-L1, may be affected most; selecting those patients who would benefit from neoadjuvant therapy is one of the frontiers for application of this type of therapy.

Neoadjuvant therapy shows great benefits, such as improved overall survival and quality of life, for patients with early-stage disease when cancer-involved organs can be salvaged, be preserved by stimulating immunity and restoring function, or not be surgically removed. Eliciting the appropriate and most effective combinations, such as doublet IO or chemotherapy combinations, is under investigation, as well as which situations would warrant postoperative continuation of the immunotherapeutic agents. This is a tremendously exciting time in locally advanced disease because a brief neoadjuvant course of IO therapy may not only demonstrate immediate benefits, but in responders, it has shown progression-free and potentially overall survival benefits.

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Benefit of Neoadjuvant Therapy Illustrated During ESMO Congress ... - Targeted Oncology

Kathleen Dorritie, MD

Assistant Professor of Medicine

University of Pittsburgh Medical Center Hillman Cancer Center

Joseph Keith Franz, MD

Hematology Oncologist

University of Pittsburgh Medical Center Hillman Cancer Center

Dhaval Rajnikant Mehta, MD

Hematology Oncologist

University of Pittsburgh Medical Center Hillman Cancer Center

Christina Maria Waters, APP

Physician Assistant

University of Pittsburgh Medical Center Hillman Cancer Center

CancerNetwork hosted a panel discussion on multiple myeloma as a part of a Satellite Sessions program focused on the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center. Experts discussed how they determine the correct treatment for patients with newly diagnosed and relapsed/refractory myeloma, including assessing the frailty and the age of a patient, the number of treatment lines a patient has received, and the benefits and consequences of using chimeric antigen receptor (CAR) T-cell therapy.

The panel included Kathleen Dorritie, MD, assistant professor of Medicine at the UPMC Hillman Cancer Center, Joseph Keith Franz, MD, a hematology oncologist, Dhaval Rajnikant Mehta, MD, a hematology oncologist, and Christina Maria Waters, APP, physician assistant.

Dorritie: Regarding the fitness of patients, what are you using to assess frailty or performance status?

Mehta: Frailty has become very patient-dependent. Certainly, I look at the comorbid conditions. The biggest thing I am looking at when deciding about the treatment is the [status of] diabetes, which medications patients are on, [their ECOG] performance status, what their social support is, etc. One of the things that has been the biggest challenge has been that patients with multiple myeloma have to come in for treatment regimens once or twice a week, so how do their transportation options and other conditions affect the decision? In terms of organ damage, are there compression fractures? Are they in significant pain? Do they have kidney failure? Those are the real factors in decision-making. We then also decide in terms of their age.

Dorritie: Have you incorporated the International Myeloma Working Group [IMWG]-frailty index in your practice?

Waters: Yes, especially in patients who are over the age of 70. You can have a very fit 75-year-old that is a candidate, but we will still utilize that tool. We do not necessarily use it for patients under 70 unless their performance status warns us to do so.

Dorritie: For patients who are frail, what is your go-to for the frontline setting?

Franz: Were blessed to have data from the phase 3 MAIA trial [NCT02252172].1 Even with a patient who is not particularly frail, theres [always a chance that the patient] may start standard therapy, get bortezomib [Velcade], [and have difficulty tolerating the treatment]. [We want] to be able to avoid bortezomib in a patient who might not do well, whos older, or who might have difficulty coming to clinic frequently. The real synergy we see between daratumumab [Darzalex] and an immunomodulatory drug [IMiDs] is just awesome. Were talking over 5 years of progression-free survival [PFS] and being seen in the clinic every couple of months. Its hard to say that this is not an awesome regimen overall.

Dorritie: In the MAIA study, there were patients up to age 90, and even those older patients can not only tolerate [treatment] but benefit from a quality-of-life perspective. Have you adopted the MAIA regimen?

Mehta: Yes, Ive been using the MAIA regimen, which is the daratumumab, lenalidomide [Revlimid], and dexamethasone [DRd] regimen, for my patients who are transplant-ineligible, with all risk statuses. Once lenalidomide became generic, I had challenges getting it, allowing me to consider the bortezomib, lenalidomide, and dexamethasone [VRd] regimen. I had to make several phone calls to [make an] appeal because the standard regimen has been DRd. Now that it became generic, regarding financial toxicities, it got to the point that I had to go to a medical monitor, share the data set, still get denied, and then go in front of a judge to appeal. This is a true story. This has been the result of maybe 1 or 2 payers who have been very stringent on it. I can probably echo some of my community oncologists who see these challenges.

Mehta: Regarding minimal residual disease [MRD] testing, there are questions about which tests to use, when to do it, etc. It is such a complex concept. MRD testing is available for multiple diseases, including chronic lymphocytic leukemia [CLL] and others. There are several companies out there that say we should be doing [MRD] in bone marrow or that we should be doing it in peripheral blood flow. What is the best way to decide how to make a treatment decision?

Dorritie: Were not quite ready for primetime there. For our in-house bone marrows, we get flow-based MRD for everybody. We can also order clonoSEQ Assay sequencing-based MRD, which is whats primarily used in clinical trials. Were not quite there yet in terms of using it to inform treatment decisions, but its something thats being studied in clinical trials.

Franz: For the first time in the phase 3 IFM 2009 trial [NCT01191060], in the post hoc analysis, we see the power of MRD, and its a great tool.2 Regardless of if a patient has had a transplant or not, the outcomes were better. There are a couple of important trials in the process that are going to help us make these decisions. The phase 2 MASTER trial [NCT03224507] was one of the first, but there are a couple more about guiding therapy, intensifying therapy, withdrawing therapy, etc.3 There are 2 validated ways to test MRD in multiple myeloma: theres high sensitivity flow cytometry, which will get you a sensitivity of 1x10-5. Then there is next-generation sequencing [NGS], which can get up to the sensitivity 1x10-6. The quality control aspects of both are important, particularly with flow cytometry. We like to see it, we like to gather the data, we like to know how deep the remission is, but right now, in terms of making decisions, I think its a little bit too early.

Dorritie: You can do it retrospectively. Oftentimes, people will have their bone marrow taken before theyre referred in, but we can use archival tissue to get their tracking sample. Then, moving forward, we could always get a fresh sample. Particularly for a patient whos struggling with [the question of], do I need to continue maintenance or do I not, it could be helpful in guiding discussions.

Mehta: When we see our patients after 2 years, and they are on dual maintenance, they want to ask, can we stop one of the drug treatments? Would you recommend using some of those MRD [results] to make a decision? Would you stop one treatment, especially the monoclonal antibodies, and just continue the oral regimen indefinitely? Or is there another way you would make your decision?

Franz: This is where we have to look at the patient and maybe break away from the convention a little bit, especially if patients are experiencing crippling adverse effects [AEs], if theres financial toxicity, or if they are in sustained MRD negative remission for years. Without strong data to support it, if we have a patient who is at standard risk who has sustained MRD negativity for years and theres a question of too much toxicity or a strong patient preference, it might be reasonable at that time to say, lets at least track this and see where we are. Thats under the presumption that this patient is going to do quite well in the long run. Are there any different practices in your clinic, based on MRD?

Waters: Typically, if a patient has had MRD negativity before the transplant, we will reassess 1 year after the transplant and then again 2 years after maintenance. If patients maintain MRD negativity, and the patient is younger or experience any of those complications, [we might give them that short break]. Recurrence may happen, but maybe the patient benefits from it long-term. At times, if MRD is negative by flow cytometry, then repeating it by clonoSEQ, the NGS test, sometimes we can remove 1 of the 2 drugs. Either the more toxic one or the less convenient one. For example, bortezomib produces some inhibitors every 2 weeks, so this could allow the patient to have some time out of the facility and not come here every 2 weeks. Especially in patients who are younger, given that this is such a chronically treated disease and knowing that this may be a decade worth of therapy, giving them a hiatus or at least some quality of life is very important. Thats where were utilizing this in clinical practice, but typically not for patients who are high risk.

Dorritie: When are you starting to think about a patient needing CAR T-cell therapy? When are you thinking about submitting a referral?

Waters: Typically, after 2 chemotherapy and immunotherapy-based regimens failed the patients, we are at least discussing [CAR T therapy] with them, potentially placing a referral, and then [discussing the options] if the next regimen is not effective enough on the disease. Currently, we have an FDA approval [of ciltacabtagene autoleucel (Carvykti; cita-cel)] for after 4 lines of therapy.4 Hopefully in the next month [idecabtagene vicleucel (Abecma; ide-cel)], we will have the ability to utilize CAR T [therapy] after 3 lines, which would allow us to capture more patients in a quicker process. The challenge with utilizing CAR T after so many lines is the manufacturing process. Sometimes we use [CAR T] in the fourth line after aphaeresis if we can get approval [from the insurance company] because we did begin in the fourth line and need to move quickly to CAR T-cell therapy.

Dorritie: Have you found it challenging to have patients come to the UPMC academic site instead of your office to receive CAR T-cell therapy?

Mehta: We as physicians who have not been fully exposed to the full CAR T treatments are still learning ourselves. As soon as a patient is becoming double or triple refractory with early progression on a maintenance treatment, I tend to call [my colleagues]. Besides the salvage options, I tend to tell my patients that the CAR T therapy has been here, and its approved. Its very promising, and we have learned a lot [about the treatment]. Toxicities are now much more tolerable. I still prep [the patients] if they are transplant-exposed, so they understand how long they have to be admitted. The challenge is with those who have never been exposed. What is the advice we should be telling our patients? Ive seen patients with lymphoma and others up to 85 years old that can handle CAR T therapy; is that true for B-cell maturation antigen [BCMA] CAR T-cell therapy? Is age a barrier? Is there any way that we should be preparing our patients in the community?

Dorritie: First and foremost, its important to stress how efficacious CAR T can be. For example, in the phase 1b/2 CARTITUDE-1 trial [NCT03548207] study leading to FDA approval, the overall response rate [ORR] was greater than 95%, which is unheard of in a heavily pretreated population.5 Similarly, in the phase 2 KarMMa study [NCT03361748] study, the ORR was [almost] in the 80% range.6 Sometimes, [you will mention this first to] patients and say, this treatment offers you benefits that a typical salvage regimen, such as selinexor [Xpovio], will not. Certainly, toxicity is a concern. We are better at managing toxicity, though. The higher-grade cytokine release syndrome [CRS] and neurologic toxicity seemed lower than in patients with lymphoma. Even though you may have a 90% rate of CRS, for most of those patients, its just a fever. Thats why its important to encourage them to come and hear about CAR T-cell therapy. Whats been your experience when talking to a patient whos been referred in for CAR T-cell therapy?

Franz: Its so well-written about. There are so many patient advocacy groups, and patient education has become very robust. I often have conversations well before a patient would even be eligible or need CAR T. Obviously, multiple ongoing studies are looking at the efficacy [of CAR T] in patients who are newly diagnosed. Itd be very interesting, in the next few months or year, if we have more options for CAR T in terms of availability and FDA approval of prior lines of therapy before patients being refractory. Its going to be a very challenging discussion and decision if CAR T is suddenly available after the first or second line of therapy.

Dorritie: Id like to discuss [what my colleagues think regarding] unmet needs and future perspectives on the treatment of patients with newly diagnosed and relapsed refractory myeloma.

Franz: It will be important to optimize patients and understand a post-BCMA relapse, whether that be bispecific antibodies or CAR T-cell therapy, and get a sense of the biology vs our other targeted agents, such as a GPRC5D therapy. Sequencing these novel immunotherapy agents is going to be critically important. We can see unprecedented efficacy with [options] like BCMA CAR T, but its not curative. The question remains, is there a role for maintenance after these types of therapies, specifically with targeted agents that are already available or other immune-based therapies, like BCMA and GPRC5D therapies together? Its important to understand how to optimize them and get the maximum benefit from each treatment.

Mehta: Myeloma is now becoming a heterogeneous disease, so trying to look for those signals and moving to more personalized treatments with genes, and MRD, or by combination of treatments, is important. One of the drugs we see signals for is venetoclax [Venclexta], and we will continue to learn more about these several options. Secondly, I will continue to work in collegiality with everyone, especially as BCMA and bispecific science continues to evolve. We have unprecedented activity, and its going to continue on to more second and third-line treatments. The third point is how treatments are eventually going to be rolled out to the community and how we can continue to make sure we are following the right follow-ups and survivorship issues as we continue to evolve with new lines of treatments.

Waters: Constant communication is important. [Treating] every patient individually is important because multiple myeloma is multiple diseases. There are variants where a patient has indolent lymphoma and was diagnosed 2 decades ago and another where a patient has undergone 3 lines of therapy in 6 months. We should take an individualized look at each patient with multiple myeloma and understand that we should not utilize all our tools too quickly just because we can. We should think about trying to maintain the longevity of the patient by working individually with each patient.

Dorritie: That seems to be the theme, how do we sequence treatment in multiple myeloma? This has been the question for the past decade with the advent of all our new therapies.

1. Bahlis N, Facon T, Usmani SZ, et. al. Daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): updated analysis of the phase 3 MAIA study. Blood. 2022;140(suppl 1):1875. doi:10.1182/blood-2019-123426

2. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311-1320. doi:10.1056/nejmoa1611750

3. Costa LJ, Chhabra S, Medvedova E, et al. Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial. Lancet Haematol. 2023;10(11):e890-e901. doi:10.1016/s2352-3026(23)00236-3

4. FDA approves ciltacabtagene autoleucel for relapsed or refractory multiple myeloma. FDA. News release. February 28, 2022. Accessed November 30, 2023. https://tinyurl.com/36utmn6z

5. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. doi:10.1016/s0140-6736(21)00933-8

6. Usmani S, Patel K, Hari P, et al. KarMMa-2 cohort 2a: Efficacy and safety of idecabtagene vicleucel in clinical high-risk multiple myeloma patients with early relapse after frontline autologous stem cell transplantation. Blood. 2022;140(Supplement 1):875-877. doi:10.1182/blood-2022-162469

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CAR T-cell Therapy Remains Preferred Options for Relapsed ... - Cancer Network

Mwanasha Merrill, hematology oncology clinical fellow, Department of Medical Oncology, Dana-Farber Cancer Institute, discusses results from a phase 2 study (NCT02362997) which evaluated PD-1 blockade post autologous stem cell transplantation with pembrolizumab (Keytruda) in patients with peripheral T-cell lymphoma (PTCL).

The study included 21 patients with PTCL and found that 83.6% (95% CI, 68-100) were progression-free at 18 months post-transplant. For the entire cohort, the overall survival rate for the entire cohort was 94.4% (95% CI, 84-100).

Merrill notes that larger studies are needed to investigate the use of PD-1 blockade and combination therapies in PTCL.

Transcription:

0:10 | In our study, we ended up with 21 patients and we had a few different PTCL histologies, but the most common was PTCL-NOS [not otherwise specified]. We found that at least 13 out of our 21 patients were progression-free at the 18 month post [transplant], so the study met the prespecified primary end point.

0:35 | We did also look at a second end point of PFS rate, and this was 83.6% when we looked at the entire cohort. We also looked at the PFS rate for the different histologies, and unfortunately, because the numbers are small, we didn't see any difference there. We also looked at the overall survival for the entire cohort that was about 94%. When we tried to look at the different histologies again, we didn't see any difference there, so we're not able to make any meaningful conclusions about that.

1:09 | We had 21 patients, so definitely a bigger study would be interesting. There's been quite a bit of data showing that PD-1 blockade, at least in NK T cells, has shown promising results in the relapsed and refractory setting. I think this would be a very attractive subtype to investigate further while exploring transplantation and then PD-1 blockade specifically for this subtype.

1:37 | Another interesting thing that can be looked at is seeing, what is the sequence? What is the ideal sequence of PD-1 blockade? Do we give it before transplant or after transplant? I say this because if we give it prior to transplant, potentially, this could act as a sensitizing agent. That's something that is worth looking at as well. Then the other thing I'll point out is just looking at combination studies. Brentuximab vedotin [Adcetris] has done so well, so looking at the combination of potentially brentuximab and PD-1 blockade with or without a transplant can be something that may be attractive as well.

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PD-1 Blockade and Transplant as a Potential New Treatment in PTCL - Targeted Oncology

Pirtobrutinib (Jaypirca) has obtained accelerated approval as a treatment for adult patients withchronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a Bruton's tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

Pirtobrutinib is a highly selective, non-covalent, or reversible, BTK inhibitor. Its unique mechanism of action allows it to be effective in patients who already undergone prior treatment with a BTK inhibitor.

"Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of [pirtobrutinib] a meaningful advance and much-needed new treatment option for these patients," William G. Wierda, MD, PhD, professor, medical director, and CLL section head for the Department of Leukemia at The University of Texas MD Anderson Cancer Center, stated in a news release from Eli Lilly, the manufacturer of pirtobrutinib."[Pirtobrutinib] offers a new treatment option and different approach to targeting BTK, providing clinical benefit for a high proportion of patients with CLL or SLL in the BRUIN Phase 1/2 trial whose disease progressed following treatment with a covalent BTK inhibitor and with a BCL-2 inhibitor."

Data from the phase 1/2 BRUIN trial (NCT03740529) informed the FDAs decision. This trial enrolled 108 patients with CLL/SLL who had been previously treated with at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. The study did not include patients who had active central nervous system (CNS) involvement or who had undergone allogeneic hematopoietic stem cell transplantation (HSCT) within 60 days.

The main end points in the trial were overall response rate (ORR) and duration of response (DOR). The ORR was 72% (95% CI, 63%-80%), with a median time to response of 3.7 months (range, 1.7-27.9). The median DOR was 12.2 months (95% CI, 9.3-14.7).

Investigators looked at a pooled analysis of the full BRUIN study population (which included disease types beyond CLL/SLL) to assess the adverse events (AEs) associated with single-agent pirtobrutinib. Overall, the most common AEs associated with treatment are decreased neutrophil count, decreased hemoglobin, fatigue, decreased lymphocyte count, musculoskeletal pain, decreased platelet count, diarrhea, COVID-19, bruising, and cough.

In the population of patients with CLL/SLL, 60% continued to receive pirtobrutinib for at least 1 year, and 14% continued for at least 2 years. The rate of AE-related dose reductions was 3.6%, the rate of interruption was 42%, and the rate of permanent discontinuation was 9%.

Of note, the median number of prior therapy lines for patients with CLL/SLL in the BRUIN trial was 5 lines (range, 2-11). Most patients had received prior ibrutinib (Imbruvica), 9% had received acalabrutinib (Calquence) , and 0.9% had received zanubrutinib (Brukinsa). Most patients (77%) discontinued prior BTK inhibitor therapy because of refractory or progressive disease.

This FDA approval the second for [pirtobrutinib] in 2023 underscores the impactful clinical benefit of continuing to leverage the BTK pathway with [pirtobrutinib] for patients with CLL or SLL as seen in the BRUIN trial, Jacob Van Naarden, chief executive officer, Loxo@Lilly, added. These first two indications for [pirtobrutinib] represent the beginning of the eventual impact that we hope [pirtobrutinib] can have for patients, and we look forward to seeing the results of the comprehensive phase 3 development program across CLL, SLL, and MCL."

Reference

Jaypirca (pirtobrutinib) now approved by U.S. FDA for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who have received at least two lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. News release. Eli Lilly and Company. December 1, 2023. Accessed December 1, 2023.https://investor.lilly.com/news-releases/news-release-details/jaypircar-pirtobrutinib-now-approved-us-fda-treatment-adult

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FDA Grants Pirtobrutinib Accelerated Approval to Treat CLL/SLL in ... - http://www.oncnursingnews.com/

Granot N, Storb R. History of hematopoietic cell transplantation: challenges and progress. Haematologica. 2020;105:271629.

Article PubMed PubMed Central Google Scholar

Spyridonidis A, Labopin M, Savani BN, Niittyvuopio R, Blaise D, Craddock C, et al. Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients. Bone Marrow Transpl. 2020;55:111425.

Article Google Scholar

Ciurea SO, Kongtim P, Varma A, Rondon G, Chen J, Srour S, et al. Is there an optimal conditioning for older patients with AML receiving allogeneic hematopoietic cell transplantation? Blood. 2020;135:44952.

Article PubMed PubMed Central Google Scholar

Eapen M, Brazauskas R, Hemmer M, Perez WS, Steinert P, Horowitz MM, et al. Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity. Blood Adv. 2018;2:2095103.

Article PubMed PubMed Central Google Scholar

Baron F, Labopin M, Peniket A, Jindra P, Afanasyev B, Sanz MA, et al. Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer. 2015;121:104855.

Article PubMed Google Scholar

Oran B, Ahn KW, Fretham C, Beitinjaneh A, Bashey A, Pawarode A, et al. Fludarabine and melphalan compared with reduced doses of busulfan and fludarabine improve transplantation outcomes in older patients with myelodysplastic syndromes. Transpl Cell Ther. 2021;27:921.e1921.e10.

Article Google Scholar

Duque-Afonso J, Finke J, Labopin M, Craddock C, Protheroe R, Kottaridis P, et al. Comparison of fludarabine-melphalan and fludarabine-treosulfan as conditioning prior to allogeneic hematopoietic cell transplantation-a registry study on behalf of the EBMT acute leukemia working party. Bone Marrow Transpl. 2022;57:126976.

Article Google Scholar

Wsch R, Reisser S, Hahn J, Bertz H, Engelhardt M, Kunzmann R, et al. Rapid achievement of complete donor chimerism and low regimen-related toxicity after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic transplantation. Bone Marrow Transpl. 2000;26:24350.

Article Google Scholar

Bertz H, Potthoff K, Finke J. Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. J Clin Oncol. 2003;21:14804.

Article PubMed Google Scholar

Spyridonidis A, Bertz H, Ihorst G, Grllich C, Finke J. Hematopoietic cell transplantation from unrelated donors as an effective therapy for older patients (> or = 60 years) with active myeloid malignancies. Blood. 2005;105:41478.

Article PubMed Google Scholar

Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, et al. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood. 2008;112:41525.

Article PubMed Google Scholar

Ciurea SO, Saliba R, Rondon G, Pesoa S, Cano P, Fernandez-Vina M, et al. Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT. Bone Marrow Transpl. 2010;45:42936.

Article Google Scholar

Ciurea SO, Saliba RM, Hamerschlak N, Karduss Aurueta AJ, Bassett R, Fernandez-Vina M, et al. Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. Leuk Lymphoma. 2012;53:9016.

Article PubMed PubMed Central Google Scholar

Majolino I, Davoli M, Carnevalli E, Locasciulli A, Di Bartolomeo P, Scim R, et al. Reduced intensity conditioning with thiotepa, fludarabine, and melphalan is effective in advanced multiple myeloma. Leuk Lymphoma. 2007;48:75966.

Article PubMed Google Scholar

Duque-Afonso J, Ihorst G, Waterhouse M, Zeiser R, Wsch R, Bertz H, et al. Impact of lung function on bronchiolitis obliterans syndrome and outcome after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning. Biol Blood Marrow Transpl. 2018;24:227784.

Article Google Scholar

Duque-Afonso J, Ihorst G, Waterhouse M, Zeiser R, Wsch R, Bertz H, et al. Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation. Bone Marrow Transpl. 2021;56:11020.

Article Google Scholar

Kanate AS, Nagler A, Savani B. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2019;2:24.

Article PubMed PubMed Central Google Scholar

Nagler A, Shimoni A Conditioning. In: Carreras E, Dufour C, Mohty M, Krger N, editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies 2019. 7th edition. Cham (CH): Springer. Chapter 13.

Passweg JR, Baldomero H, Chabannon C, Basak GW, de la Cmara R, Corbacioglu S, et al. Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant. 2021;56:165164.

Article PubMed PubMed Central Google Scholar

Saraceni F, Scortechini I, Fiorentini A, Dubbini MV, Mancini G, Federici I, et al. Conditioning regimens for frail patients with acute leukemia undergoing allogeneic stem cell transplant: how to strike gently. Clin Hematol Int. 2021;3:15360.

Article PubMed PubMed Central Google Scholar

Rambaldi A, Grassi A, Masciulli A, Boschini C, Mic MC, Busca A, et al. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015;16:152536.

Article PubMed Google Scholar

Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C, et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transpl. 2002;8:46876.

Article Google Scholar

de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004;104:85764.

Article PubMed Google Scholar

Beelen DW, Stelljes M, Remnyi P, Wagner-Drouet EM, Dreger P, Bethge W, et al. Treosulfan compared with reduced-intensity busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: final analysis of a prospective randomized trial. Am J Hematol. 2022;97:102334.

Article PubMed Google Scholar

Shimoni A, Hardan I, Shem-Tov N, Rand A, Herscovici C, Yerushalmi R, et al. Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan. Leukemia. 2007;21:210916.

Article PubMed Google Scholar

Bernardo ME, Zecca M, Piras E, Vacca A, Giorgiani G, Cugno C, et al. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in patients with thalassaemia major. Br J Haematol. 2008;143:54851.

Article PubMed Google Scholar

Bernardo ME, Piras E, Vacca A, Giorgiani G, Zecca M, Bertaina A, et al. Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood. 2012;120:4736.

Article PubMed Google Scholar

Finke J, Schmoor C, Stelljes M, Burchert A, Dreger P, Hegenbart U, et al. Thiotepa-fludarabine-treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial. Bone Marrow Transpl. 2022;57:166470.

Article Google Scholar

Sanz J, Boluda JC, Martn C, Gonzlez M, Ferr C, Serrano D, et al. Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen. Bone Marrow Transpl. 2012;47:128793.

Article Google Scholar

Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R, et al. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121:84957.

Article PubMed Google Scholar

Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transpl. 2013;19:11722.

Article Google Scholar

Sora F, Grazia CD, Chiusolo P, Raiola AM, Bregante S, Mordini N. et al. Allogeneic hemopoietic stem cell transplants in patients with Acute Myeloid Leukemia (AML) prepared with Busulfan and Fludarabine (BUFLU) or Thiotepa, Busulfan, and Fludarabine (TBF): a retrospective study. Biol Blood Marrow Transpl. 2020;26:698703.

Article Google Scholar

Saraceni F, Labopin M, Hamladji RM, Mufti G, Soci G, Shimoni A, et al. Acute leukemia working party of the European society for Blood and Marrow Transplantation (EBMT). Thiotepa-busulfan-fludarabine compared to busulfan-fludarabine for sibling and unrelated donor transplant in acute myeloid leukemia in first remission. Oncotarget. 2017;9:337993.

Article PubMed PubMed Central Google Scholar

Craddock C, Jackson A, Loke J, Siddique S, Hodgkinson A, Mason J, et al. Augmented reduced-intensity regimen does not improve postallogeneic transplant outcomes in acute myeloid leukemia. J Clin Oncol. 2021;39:76878.

Article PubMed Google Scholar

Marsh RA, Lane A, Mehta PA, Neumeier L, Jodele S, Davies SM, et al. Alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following alemtuzumab, fludarabine, and melphalan RIC HCT. Blood. 2016;127:50312.

Article PubMed Google Scholar

Bertz H, Spyridonidis A, Wsch R, Grllich C, Egger M, Finke J. A novel GVHD-prophylaxis with low-dose alemtuzumab in allogeneic sibling or unrelated donor hematopoetic cell transplantation: the feasibility of deescalation. Biol Blood Marrow Transpl. 2009;15:156370.

Article Google Scholar

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