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Sirolimus is an acceptable alternative to tacrolimus for graft-versus-host disease prophylaxis after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide
Elmariah, H., Otoukesh, S., Kumar, A., Ali, H., Arslan, S., Shouse, G., Pourhassan, H., Nishihori, T., Faramand, R., Mishra, A., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy), tacrolimus (TAC) and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor transplantation. A phase II study from Moffitt Cancer Center substituting sirolimus (SIRO) in place of TAC reported comparable rates of grade II-IV acute GVHD. Many centers have substituted SIRO for TAC in this setting based on a preferred side effect profile, though comparative data is limited. OBJECTIVE The objective of this study is to compare outcomes of haplo HCT with PTCy/SIRO/MMF versus PTCy/TAC/MMF. STUDY DESIGN We retrospectively compared haplo HCT outcomes with PTCy/SIRO/MMF versus PTCy/TAC/MMF. Included were all consecutive patients receiving haplo donor T cell replete peripheral blood stem cell graft HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. RESULTS A total of 423 patients were included, of which 84 (20%) received SIRO and 339 (80%) received TAC. Median age for all patients was 54 (range 18 to 78) years, and median follow-up for entire study cohort was 30 months. SIRO group had a higher proportion of patients ≥60 years (58% versus 34%, P = <.01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV acute GVHD (45% versus 47%, P = .6) at day +100 or chronic GVHD (47% versus 54%, P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better with TAC (OR = 0.30, CI 0.1 to 0.83, P = .02) with a median time to engraftment of 17 days versus 18 days for SIRO, but platelet engraftment was similar in both groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on acute or chronic GVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease free survival, or overall survival after peripheral blood haplo HCT. CONCLUSIONS These findings suggest that SIRO is a comparable alternative to TAC in combination with PTCy/MMF for GVHD prophylaxis, resulting in overall similar clinical outcomes despite delay in engraftment after peripheral blood haplo HCT. While TAC remains the standard of care, SIRO may be substituted based on the side effect profile of these medications with consideration of patient medical comorbidities at HCT.
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ASTCT Clinical practice recommendations for transplant and cellular therapies in diffuse large B-cell lymphoma
Epperla, N., Kumar, A., Abutalib, S. A., Awan, F. T., Chen, Y. B., Gopal, A. K., Holter-Chakrabarty, J., Kekre, N., Lee, C. J., Lekakis, L., et al
Transplantation and cellular therapy. 2023
Abstract
Autologous hematopoietic cell transplantation (auto-HCT) has long remained the standard approach for patients with relapsed/refractory (R/R) chemosensitive diffuse large B-cell lymphoma (DLBCL). However, the advent of chimeric antigen receptor (CAR) T-cell therapy has caused a paradigm shift in the management of R/R DLBCL patients, especially with the recent approval of CD19-directed CAR T-cell therapy in the second line setting in high-risk groups (primary refractory and early relapse [≤12 months]). Consensus on the contemporary role, optimal timing, and sequencing of HCT and cellular therapies in DLBCL is lacking. Therefore, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines undertook this project to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 20 consensus statements with a few key statements as follows: 1) in the first-line setting, there is no role of auto-HCT consolidation for those achieving complete remission (CR) following R-CHOP or similar therapy in non-double hit/triple hit cases (DHL/THL) and in DHL/THL cases receiving intensive induction therapies, but auto-HCT may be considered in eligible patients receiving R-CHOP or similar therapies in DHL/THL cases. 2) Auto-HCT consolidation with thiotepa-based conditioning is standard-of-care for eligible patients with primary central nervous system achieving CR with first-line therapy. 3) In the primary refractory and early relapse setting, the preferred option is CAR T-cell therapy, while in late relapse (>12 months), consolidation with auto-HCT is recommended in those achieving chemosensitivity to salvage therapy (CR or partial response), and CAR T-cell therapy is recommended in those not achieving remission. These clinical practice recommendations will serve as a tool to guide clinicians managing patients with newly diagnosed and R/R DLBCL.
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3.
Predictors of lenalidomide maintenance duration after autologous stem cell transplant in patients with multiple myeloma
Rath, C., Yoo, C., Cheplowitz, H., Lo, M., Young, R., Guglielmo, J., Saunders, I. M., Banerjee, R., Young, R., Kumar, A., et al
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2023;:10781552221150935
Abstract
BACKGROUND For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. Because longer durations of lenalidomide maintenance are associated with improved survival, identifying strategies to avoid premature cessation of maintenance is an important priority in the post-transplant setting. OBJECTIVES The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management. Key secondary objectives included predictors of intolerable toxicity, rationale for lenalidomide dose reduction/discontinuation, and characterization of dose adjustments. STUDY DESIGN This retrospective, multi-center cohort study included adults with MM who underwent auto-SCT and initiated maintenance lenalidomide between 01/01/2012 and 02/28/2021. Variables assessed as potential predictors of maintenance duration or intolerable toxicity included age, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status at time of auto-SCT, renal function, initial lenalidomide dose, use of combination maintenance therapy, and cytogenetic risk category. RESULTS Among 299 patients included, the median age at time of auto-SCT was 62 years (range 30-77). The majority of patients had standard-risk cytogenetics (64%) and an ECOG performance status of 0 or 1 (72%). In the overall population, the median duration of maintenance was 1.3 years (range 0.3-8.6 years). The median initial dose of lenalidomide was 10 mg daily (range 2.5-25 mg). During the study period, 35% of patients had a dose reduction due to toxicity, 21% stopped lenalidomide due to disease progression, and 19% stopped due to toxicity. Multivariate linear regression analyses did not identify any significant predictors of lenalidomide duration or discontinuation due to intolerable toxicity. The most frequently reported toxicities leading to discontinuation were cytopenias, rash, and fatigue. CONCLUSION This analysis did not identify any significant risk factors to predict the duration of lenalidomide maintenance or discontinuation for toxicity following auto-SCT in patients with MM. While limited by the retrospective design and relatively small sample size, our findings suggest that a priori lenalidomide dose reductions based on patient co-morbidities or performance status may not substantially affect the duration of lenalidomide maintenance.
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Age Impacts Risk of Mixed Chimerism Following RIC HCT for Non-SCID Inborn Errors of Immunity
Fitch, T., Lane, A., McDonnell, J., Bleesing, J., Jordan, M., Kumar, A., Khandelwal, P., Khoury, R., Marsh, R., Chandra, S.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Alemtuzumab, fludarabine and melphalan containing reduced intensity conditioning (RIC) is commonly used in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for definitive treatment of high-risk inborn errors of immunity (IEI). Although survival is favorable, there is increased risk of mixed chimerism leading to secondary graft failure. OBJECTIVES Evaluate factors associated with risk of developing mixed chimerism, particularly the influence of age in patients undergoing allogeneic HCT for non-SCID IEI who received a uniform RIC regimen that included intermediate schedule alemtuzumab, fludarabine and melphalan. We hypothesized that age would impact incidence of mixed chimerism. STUDY DESIGN We retrospectively reviewed records of patients who underwent HCT for non-SCID IEIs with a uniform RIC regimen that included intermediate schedule alemtuzumab (1 mg/kg divided over days -14 to - 10), fludarabine (150 mg/m2 or 5 mg/kg if weight <10 kg divided over days -9 to -4), and melphalan (140 mg/m2 or 4.7 mg/kg if weight <10 kg on day-3) between 2010 and 2020 at our institution. Mixed chimerism was defined as <95% donor on 2 or more consecutive occasions on whole blood. RESULTS Ninety-three patients who underwent RIC-HCT for non-SCID IEI using intermediate schedule alemtuzumab, fludarabine, and melphalan were evaluated and categorized into 3 groups: <1, 1-5, and > 5 years of age. Forty-nine patients (52.7%) developed mixed chimerism at a median of 34 days post-HCT (range, 10-1396 days). Mixed chimerism developed in 88.9 % (n=16/18) for <1 year, 57.1% (n=20/35) for 1-5 years, and 35% (n=14/40) for those >5 years. Patients <5 years of age were significantly more likely to develop mixed chimerism (X(2) (3, N = 93) = 14.8, p =0.001). We observed a significantly increased cumulative incidence of developing mixed chimerism if < 1 year of age (p=0.0002). Competing risk regression analysis demonstrated an increase in odds of development of mixed chimerism for age <1 (OR 3.72, p = 0.006, 95% CI 1.46-19.46) compared to age >5 years and decrease in odds of mixed chimerism in patients who developed acute GVHD prior to any intervention (OR 0.24, p=0.005, 95% CI 0.09-0.65) There was no significant association between mixed chimerism and graft source, graft type, CD34+ or CD3+ cell dose, HLA match or underlying disease (HLH vs non-HLH). Additionally, the need for secondary intervention was evaluated; 27 patients (29.0%) required one or more secondary intervention(s) (DLI, CD34 Boost, or second HCT). Patients <1 year of age with mixed chimerism were significantly more likely to require secondary intervention for mixed chimerism than patients > 5 years (p =0.004). CONCLUSION Our study demonstrates that young age <5 years, especially age <1 year is associated with an increased risk of developing mixed chimerism in patients undergoing RIC-HCT for non-SCID IEI using intermediate schedule alemtuzumab, fludarabine, and melphalan. Our data suggest tailoring regimen intensity based on age to reduce the incidence of mixed chimerism. Children <5 years, particularly those <1 year of age, require a higher intensity regimen. Possible strategies include adding thiotepa or using a busulfan-based reduced toxicity regimen.
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Autologous hematopoietic cell transplantation versus whole-brain radiotherapy consolidation in primary central nervous system lymphoma: A systematic review and meta-analysis
Epperla, N., Reljic, T., Chowdhury, S. M., Ferreri, A. J. M., Kumar, A., Hamadani, M.
Hematological oncology. 2022
Abstract
The management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes administration of high-dose methotrexate based regimens followed by consolidation therapy to minimize the risk of relapse. However, the best consolidation strategy (autologous hematopoietic cell transplant [auto-HCT] vs. whole-brain radiotherapy [WBRT]) is controversial. Hence, we performed a systematic review and meta-analysis of all randomized controlled trials that compared auto-HCT versus WBRT consolidation for patients with PCNSL after first-line treatment.The primary outcome was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), response rates (overall response rate [ORR] and complete remission [CR]), relapse rate, treatment-related mortality (TRM), and neuropsychological adverse events. We performed a pooled analysis of the single-arm studies that incorporated auto-HCT or WBRT consolidation and evaluated neurocognitive outcomes. Only two studies met the inclusion criteria (n = 240). There was no significant difference in OS (HR = 1.50; 95% CI = 0.95-2.36), PFS (HR = 0.99; 95% CI = 0.44-2.22), ORR (RR = 1.48; 95% CI = 0.90-2.44), CR rate (RR = 1.21; 95% CI = 0.90-1.63), relapse rate (RR = 0.46; 95% CI = 0.05-4.28), and TRM (RR = 5.67; 95% CI = 1.01-31.91). The neuropsychological tests to assess neurocognitive domains were different and inconsistently reported in the two studies and therefore we were unable to perform a meta-analysis but provide a descriptive assessment. Both the studies showed a significant decline in the attention/executive function (based on the trail making test A and trail making test B) in those receiving WBRT compared to auto-HCT. We found 9 single-arm phase II studies that reported data on outcomes associated with either auto-HCT (5 studies) or WBRT (4 studies) consolidation. Of these, two studies (n = 43) reported data on neurocognitive decline following auto-HCT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 6% (95% CI, 0%-17%) for those receiving auto-HCT and there was no heterogeneity between studies (I(2) = 0%). Three studies (n = 122) reported data on neurocognitive decline following WBRT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 43% (95% CI, 11%-78%) for those receiving WBRT and there was high heterogeneity between studies (I(2) = 94%). There was significant heterogeneity between subgroups (p = 0.035). The outcomes were not significantly different in patients with PCNSL receiving auto-HCT or WBRT consolidation therapies, however, there is a higher degree of neurocognitive decline associated with WBRT compared to auto-HCT consolidation. The decision to choose a consolidation strategy needs to be individualized based on age, frailty, and co-morbidities.
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Long-Term Outcomes and Safety Trends of Autologous Stem-Cell Transplantation in Non-Hodgkin Lymphoma: A Report From A Tertiary Care Center in India
Kumar, S., Sharma, A., Pramanik, R., Pathak, N., Gogia, A., Kumar, A., Kayal, S., Sharma, V., Sahoo, R. K., Thulkar, S., et al
JCO global oncology. 2022;8:e2100383
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Abstract
PURPOSE Published experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India. PATIENTS AND METHODS We retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B). RESULTS Overall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT. CONCLUSION It is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.
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Efficacy of a second allogeneic hematopoietic cell transplant in relapsed acute myeloid leukemia: results of a systematic review and meta-analysis
Kharfan-Dabaja, M. A., Reljic, T., Yassine, F., Nishihori, T., Kumar, A., Tawk, M. M., Keller, K., Ayala, E., Savani, B., Mohty, M., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only known treatment modality that can offer the possibility of cure for acute myeloid leukemia (AML). Unfortunately, relapse and/or disease progression still occurs in over one-third of cases even when patients are allografted in complete hematologic remission (CR). Treatment of AML relapsing after a first allo-HCT is particularly challenging. A second allo-HCT is offered to patients considered fit for the procedure, but reported outcomes have been conflicting. OBJECTIVES To perform a systematic review and meta-analysis to assess the totality of evidence on the role of a second allo-HCT in patients with AML. STUDY DESIGN AND METHODS We performed a comprehensive literature search using PUBMED/MEDLINE and EMBASE on August 25, 2021 and extracted clinical outcome data relating to benefits (CR, overall survival [OS], and progression-free/disease-survival [PFS/DFS]) and harms (acute and chronic graft-versus-host disease [GVHD], non-relapse mortality [NRM] and relapse). RESULTS The search identified 821 studies. Only 20 studies (n= 2,772 patients) met our inclusion criteria. A second allo-HCT resulted in pooled CR, OS, PFS/DFS, NRM and relapse rates of 67%, 34%, 30%, 27%, and 51%, respectively. OS was 2-fold higher when the second allo-HCT was performed in CR (38% vs. 17%) and 3-fold higher in patients who had a later relapse from the first allo-HCT (34% vs. 10%). There was no apparent difference in pooled OS (HR=1.01 (95%CI=0.78-1.31), p=0.94) whether the same original donor or a different one was used. CONCLUSION Notwithstanding several limitations apart from the high heterogeneity among included studies, this analysis shows that a second allo-HCT is a reasonable treatment option for relapsed AML. The procedure appears to be more effective when performed in CR and in patients who had a later relapse from the first allo-HCT. The high pooled relapse rates exceeding 50%, even when receiving the second allo-HCT in CR is worrisome and emphasizes the need to incorporate new therapies whether as post-transplant maintenance or consolidation, to mitigate relapse risk. This analysis was limited to patients receiving a second allo-HCT for the sole purpose of treating AML relapse. Accordingly, we caution against extrapolating these findings to other indications such as treatment of graft failure, poor graft function or mixed donor chimerism.
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Outcomes Following Intolerance to Tacrolimus/Sirolimus Graft-Versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation
Mirza, A. S., Tandon, A., Jenneman, D., Cao, S., Brimer, T., Kumar, A., Kidd, M., Khimani, F., Faramand, R., Mishra, A., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Although tacrolimus and sirolimus (TAC/SIR) is an accepted graft-versus-host disease (GVHD) prophylaxis following allogeneic hematopoietic cell transplant (HCT), toxicity from this regimen can lead to premature discontinuation of immunosuppression. There are limited studies reporting outcomes and subsequent treatment of patients with TAC/SIR intolerance. OBJECTIVES To assess outcomes of patients with TAC/SIR intolerance and guide subsequent management after intolerance. STUDY DESIGN We retrospectively analyzed transplant outcomes of consecutive adult patients at Moffitt Cancer Center who received allogeneic HCT with TAC/SIR as GVHD prophylaxis from 2009 to 2018. TAC/SIR intolerance was defined as discontinuation due to toxicity of either TAC or SIR before post-transplant day 100. RESULTS 777 patients met the inclusion criteria. Median follow-up was 22 (0.2-125) months. Intolerance occurred in 13% (n = 104) of patients at a median of 30 (range 5-90) days. The most common causes of intolerance were acute kidney injury (n = 53 [51%]), thrombotic microangiopathy (n = 31 [28%]), and veno-occlusive disease (n = 23 [22%]). The cumulative incidence of grade 2 to 4 acute GVHD at 100 days in TAC/SIR-intolerant patients was 50% (95% CI, 39%-64%) and 25% (95% CI, 22%-29%) in patients tolerant to this regimen (P < .0001). In multivariate analyses, grade 2 to 4 acute GVHD was significantly higher in TAC/SIR-intolerant patients (HR 2.40; 95% CI, 1.59-3.61; P < .0001). Similarly, in multivariate analyses, TAC/SIR-intolerant patients had more chronic GVHD (HR 1.48, 95% CI, 1.03-2.12; P = .03). The non-relapse mortality (NRM) at 1 year in TAC/SIR-intolerant patients was 47% (95% CI, 38%-59%) and 12% (95% CI, 10%-15%) in those tolerant to the regimen (P < .0001). The 2-year relapse free survival of TAC/SIR-intolerant patients was 35% (95% CI, 25%-44%) and 60% (95% CI, 57%-65%) among TAC/SIR-tolerant patients, (HR 2.30; 95% CI, 1.61-3.28; P < .0001). Intolerance stratified by early (≤30 days) versus late (31-100 days) significantly affected the cumulative incidence of acute GVHD at 75% (early [95% CI, 59%-94%]) versus 33% ([late] 95% CI, 21%-50%) (P = .001) as well as the cumulative incidence of NRM at 61% ([early] 95% CI, 48%-77%) versus 35% ([late] 95% CI, 24%-51%) (P = .006). After developing TAC/SIR intolerance, most patients were switched to an alternative 2-drug regimen (71/104 [68%]), with the most common being mycophenolate mofetil in addition to continuing TAC or SIR (68/71 [96%]). CONCLUSIONS Overall, TAC/SIR intolerance was associated with poorer outcomes. Early intolerance contributed to higher risk of acute GVHD, increased NRM, and inferior survival. Patients with early intolerance were often switched to an alternative agent, and patients with late intolerance tended to be continued on single-drug therapy without substitution. Single-drug versus 2-drug regimens after intolerance did not appear to affect outcomes. Management strategies to mitigate the risks of intolerance are warranted.
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ASTCT Committee on Practice Guidelines Survey on Evaluation & Management of Diffuse Large B-cell Lymphoma after failure of Chimeric antigen receptor T cell therapy (CAR-T) therapy
Ahmed, N., Kumar, A., Kharfan-Dabaja, M. A., DeFilipp, Z., Herrera, A., Hashmi, S., Dholaria, B., Perales, M. A., Carpenter, P. A., Hamadani, M.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Chimeric antigen receptor T cell therapy (CAR-T) is a major advance in managing aggressive relapsed and/or refractory B-cell lymphomas; however, relapses are frequent and pose a major therapeutic challenge. There is substantial variability across transplant and cellular therapy programs in assessing and managing post-CAR-T failures. METHODS The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines conducted an online cross-sectional survey between August 2021 and October 2021, to determine the U.S. lymphoma and transplant and cellular therapy physicians' practice patterns for the detection and diagnosis of CAR-T failure, and management strategies for diffuse large B cell lymphoma (DLBCL) in this particular setting. RESULTS Email surveys were sent to 901 potential participants, of which 174 (19%) completed the survey. Responders were mainly White (51.2%), male (70.7%), and with >10 years of practice experience (51.2%). 87% of the responders were affiliated with university/teaching centers; 54.6% had general oncology practices and 45.4% had lymphoma-focused transplant/cellular therapy practices. The most common periods to perform surveillance scans were at 3 months and 12 months after CAR-T infusion. 88.5% of responders would often or always consider a biopsy to confirm relapse and 89% would routinely check for the persistence of the antigen targeted by the CAR (e.g. CD19 in the case of CD19 CAR-T). The most popular first salvage regimen for relapse or progression was an alternate CAR-T therapy (dual or alternate target) regardless of CD19 positivity. 27% of responders chose this regimen for CD19 positive relapse, while 31% of responders did so for CD19 negative relapse. 88.5% of responders favored consolidative allogeneic hematopoietic cell transplantation (alloHCT) after response to salvage, whereas 51.2% of physicians would consider autologous hematopoietic cell transplant (AHCT) in transplant naïve patients. CONCLUSIONS There is substantial cross-center variation in surveillance, diagnosis, and management of CAR-T failure. Prospective clinical trials evaluating novel agents in this setting are urgently needed to identify best management strategies.
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10.
ASTCT Clinical Practice recommendations for transplant and cellular therapies in multiple myeloma
Dhakal, B., Shah, N., Kansagra, A., Kumar, A., Lonial, S., Garfall, A., Cowan, A., Poudyal, B. S., Costello, C., Gay, F., et al
Transplantation and cellular therapy. 2022
Abstract
Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape. The American Society for Transplantation and Cellular Therapy (ASTCT) convened an expert panel to formulate clinical practice recommendations for role, timing, and sequencing of autologous (auto-HCT), allogeneic (allo-HCT) and CAR T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The RAND-modified Delphi method was used to generate consensus statements. Twenty consensus statements were generated. The panel endorsed continued use of auto-HCT consolidation for patients with NDMM as a standard-of-care option, whereas in the front line allo-HCT and CAR-T were not recommended outside the setting of clinical trial. For patients not undergoing auto-HCT upfront, the panel recommended its use in first relapse. Lenalidomide as a single agent was recommended for maintenance especially for standard risk patients. In the RRMM setting, the panel recommended the use of CAR-T in patients with 4 or more prior lines of therapy. The panel encouraged allo-HCT in RRMM setting only in the context of clinical trial. The panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MM.