Single Autologous Stem Cell Transplantation Research Articles

Efficacy of Combined Drug Pre-transplant Conditioning Regimens in Multiple Myeloma Patients with Single Autologous Hematopoietic Stem Cell Transplantation

Aim. To conduct an interim outcome analysis of conditioning regimens with carfilzomib or thiotepa compared to standard melphalan 200 mg/m2 regimen in multiple myeloma (MM) patients with single autologous hematopoietic stem cell transplantation (auto-HSCT).
 Materials & Methods. The retrospective analysis focused on outcomes of 67 single auto-HSCTs performed from 2017 to 2021. Responses as well as progression-free (PFS) and overall survival (OS) rates were compared in MM patients per IWMG criteria in pre- and post-transplant periods. Three conditioning regimens were assigned: melphalan 200 mg/m2 (Mel200), melphalan/carfilzomib combination (Mel/Karfil), and melphalan/thiotepa combination (Mel/Thio). In an additional cohort of 12 MM patients, next-generation sequencing assay was used to detect inherited and somatic mutations associated with proteasome inhibitor efficacy. For this purpose, DNA of peripheral blood lymphocytes and bone marrow plasma cells were examined.
 Results. PFS medians were comparable in MM patients treated with Mel200 (n = 40) and Mel/Karfil (n = 10) conditioning regimens, they were 32 and 23 months, respectively (p = 0.241). In these cohorts, OS median was not reached, and the curves showed no significant differences (p = 0.050). Out of 10 MM patients treated with Mel/Karfil, six received melphalan 140 mg/m2, the remaining 4 patients received 200 mg/m2. Complete response (CR) rate in the Mel200 and Mel/Karfil groups increased two-fold after auto-HSCT: from 35.5 % to 74.2 % and from 25.0 % to 50.0 %, respectively. The worst PFS and OS medians were in the Mel/Thio group, i.e., 12 and 17 months, respectively, and CR rate after auto-HSCT remained unchanged. The best PFS was associated with CR rather than very good partial or partial response after auto-HSCT, they were 48, 21, and 23 months, respectively (p = 0.001). Exome sequencing of DNA of peripheral blood lymphocytes and bone marrow plasma cells revealed polymorphic variants in the genes associated with chemotherapy response.
 Conclusion. The outcomes of Mel/Karfil, the regimen containing the reduced dose of melphalan 140 mg/m2, and the statistical comparability with the Mel200 regimen suggest that this combination can be effective in the treatment of MM patients with impaired renal function, which still needs to be further confirmed. No advantage of the combined conditioning regimen over the standard one can be accounted for by the loss of plasma cell sensitivity to proteasome inhibitors. The obtained data provide ground for modifying the study protocol with a particular focus on evaluating the efficacy and safety of conditioning regimen Mel/Karfil with melphalan 200 mg/m2 depending on biologic phenotype of plasma cell.

Incidence of Secondary Primary Malignancies after Long-Term Follow up of Multiple Myeloma Patients Treated with Autologous Stem Cell Transplantation - Report from Croatian Cooperative Group for Hematologic Malignancies (KroHem)

Background: Autologous stem cell transplantation (ASCT) after induction treatment is standard of care for multiple myeloma (MM) for the last 30 years. Two transplantations up-front (so-called tandem transplant) were standard of care for all MM patients. With the use of new antimyeloma agents (such as proteasome inhibitors, immunomodulators and especially monoclonal antibodies) this approach has changed and tandem transplant is now reserved mainly for patients with high-risk disease, defined by revised international staging system (R-ISS). There have been reports which cast further doubts on the value of the more aggressive tandem ASCT approach, as well as reports suggesting higher incidence of secondary primary malignancies (SPM) after high dose therapy and ASCT. Aims: To describe long-term outcomes of MM patients treated with ASCT (single, delayed, and tandem) and the rate of secondary primary malignancies. Methods: a retrospective analysis of outcomes of 577 MM patients who underwent 865 ASCT procedures between 1993 and 2017 was performed. Data were collected from 3 transplant centres and 9 other haematological centres in which MM patients were treated pre- and post-transplant. During that period treatment strategies changed significantly from single to tandem to salvage second ASCT. Results: there were 577 patients included. Median age at first transplant was 58 years (range 22 - 74). There were 295 female and 282 male patients. 346 patients received VAD (vincristine, doxorubicin, dexamethasone) and 231 received bortezomib and/or thalidomide (PI/IMiD) based regiments as induction therapy. All patients received high dose melphalan for pretransplant conditioning, 32 in combination with total body irradiation. Tandem ASCT (defined as second transplantation performed within 6 months after the first) was performed in 226 patients, single ASCT in 262 and salvage second (after relapse and/or progression) in 89 patients. Median overall survival (OS) for the entire group is 81.9 months and median progression free survival (PFS) 38.9 months. Tandem ASCT in comparison to single and second salvage transplantation resulted in statistically significant better OS (115 vs. 83 vs. 67 months respectively, p < 0.0001) and PFS (48 vs. 32. vs. 28 months respectively, p < 0.0001). There was no difference in outcomes regarding type of induction therapy, VAD vs. PI/IMiD based: median OS was 83 vs. 80 months, respectively (p=0.39) and median PFS was 39 vs. 38 months, respectively (p=0.15). 17.6% percent of patients who were treated with tandem ASCT are progression-free more than 10 years after the procedure while 10-year OS is 31.9%. 51 patients (8.8%) developed secondary malignancies (SPM). Most common SPM were lung carcinoma (10 patients), colorectal carcinoma (7 patients), myelodysplastic syndrome/acute myeloid leukaemia (6 patients), breast carcinoma (4 patients) and melanoma (4 patients). Of those 19 died due to SPM (3% of the entire patient group). There was no correlation between number of ASCT and SPM (p=0.87). Conclusion: in our group of patients tandem ASCT resulted in superior OS and PFS in comparison to single and/or salvage ASCT. Interestingly, we did not observe benefit of new drugs (PI/IMiD) in induction therapy regarding outcomes. This peculiar result might be due to rather late availability of these drugs in front line settings (bortezomib and thalidomide since 2015) and time period taken for analysis (up to 2018). SPM rate was similar to other reports and did not show significant correlation with number of ASCT. More than 15% of patients treated with tandem ASCT experienced very prolonged PFS and almost 32% had OS longer than 10 years.

Lenalidomide Maintenance after VTD Induction and Autologous Stem Cell Transplantation: An Italian Real-Life Study of 558 Patients

According to 2021 ESMO guidelines, treatment of newly diagnosed (ND) transplant eligible (TE) Multiple Myeloma (MM) patients is settled by an induction phase followed by single or tandem autologous stem cell transplantation (ASCT) and Lenalidomide (Len) maintenance. Len maintenance was approved in Italy in May 2018 due to the results of the meta-analysis by McCarthy et al. of three large randomized clinical trials. Before the approval of daratumumab-bortezomib-thalidomide-dexamethasone (D-VTD) regimen, VTD triplet combination was the most used induction regimen across Italian centers. In addition, given the data from the EMN02 trial, in the last years tandem ASCT has been a consolidated practice especially for high-risk cytogenetic patients. However, only a minority of patients enrolled in the meta-analysis of McCarthy received VTD induction and in most of them a single ASCT has been performed. In this context, the aim of this real-life study was to evaluate the efficacy and the safety of Len maintenance after VTD plus single or tandem ASCT in ND TE MM patients. The study cohort included 558 patients with a median age of 59 years (24-74) followed in 21 Italian referral centers. Baseline clinical and biological features are reported in table 1. ISS III and R-ISS III were detected in 111/518 (21.4%) and 44/405 (10.9%) cases, respectively, moreover, 30/327 (9.2%) patients showed R2 ISS stage IV. FISH analysis was available in 408 patients with 70 of them displaying high risk (HR) alterations [including t(4;14), t(14,16) and del17p]. Among the 338 standard risk patients, information about 1q status was available for 320 of them, with 60 patients harboring +1q abnormalities (18.75%). All patients received VTD induction (median number of cycles 4) and single or tandem ASCT was performed in 63.7% and 36.3% of cases, respectively. A median number of 22 cycles of Len maintenance was administered. Complete response (CR) and stringent CR (sCR) rates before starting Len were 31.8% and 14.2%, respectively (overall 46%) and increased with maintenance to 39.6% and 16.6%, respectively (overall 56.2%). Most importantly, 2-year CR and sCR rates in evaluable patients were superimposable (40.6% and 14.9% respectively, 55.5% overall). One hundred ninety-seven patients (35.3%) discontinued treatment, mostly due to progressive disease (134/197, 68.0%). Toxicities were mostly hematological with neutropenia found in 50.4% of cases (grade ≥3 in 17.2%), followed by thrombocytopenia and anemia in 24.4% and 16.1% of cases, respectively (grade ≥3 in 2.1% and 1.8% of cases, respectively). Non-hematological adverse events were primarily gastrointestinal (31.2%, grade ≥3 in 2.3%) and infections (42.3%, grade ≥3 in 3.9%) while skin related disorders affected 7.9% of patients. With a median follow up of 30 months, the 2-year PFS and OS from starting maintenance were 80.6% and 96.7%, respectively. No significant PFS difference was found according to age (>65 years vs ≤65 years, p=0.5924) or ASCT (single vs tandem, p=0.4694). Patients with low-risk disease including ISS I and R-ISS I showed improved PFS as compared to patients with ISS >I and R-ISS >I (2y PFS 84.6% vs 76.6%, p=0.0587 and 87.8% vs 72.7%, p=0.0195, respectively). By R2-ISS, low risk disease (R2-ISS I) confirmed a better outcome as compared to R2-ISS II-III (2y PFS 88.9% vs 72.2%, p=0.0333) and to R2-ISS IV (2y PFS 47.2%, p<0.0001). Finally, considering cytogenetic risk status, standard risk patients displayed a significantly prolonged PFS as compared to high-risk patients (2y PFS 81.6 % vs 56.3%, p<0.0001) and an improved although not significant outcome than patients harboring isolated +1q (2y PFS 77.2%, p=0.09). Moreover, we demonstrated that the accumulation of HR cytogenetic abnormalities reduces patients' outcome, in detail the PFS of patients with at least 2 HR abnormalities was significantly lower than patients with only 1 and without HR aberrations, respectively [2y PFS 44.8% (≥2) vs 73.5% (1), p=0.0301, and 2y PFS 44.8% (≥2) vs 82.8% (0), p<0.0001, figure 1]. To our knowledge, this is the first study evaluating the safety and efficacy of Len maintenance after VTD plus single or tandem ASCT. Our results provide evidence that patients with clinical and biological low risk disease, and more specifically those with R2- ISS I, benefit the most from Len maintenance with a favorable safety profile.

Real-world results of autologous stem cell transplantation in newly diagnosed multiple myeloma: a report from the Canadian Myeloma Research Group database

Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients as part of initial therapy. Using the Canadian Myeloma Research Group (CMRG) national database, we examined the details and outcomes of ASCT performed as first-line therapy in eligible Canadian MM patients between 2007 to 2021. We included 3821 patients with 72% receiving CyBorD induction and 2061 patients receiving maintenance, consisting of lenalidomide +/- steroids in 78.3%. The median PFS and OS for patients given a single ASCT were 35.4 and 126 months. Those receiving a second induction regimen had significantly inferior outcomes, although when maintenance was used, results were comparable regardless of the number of induction regimens administered (median PFS 55.3 vs 51.1 months [p = 0.11]; median OS 158.6 vs not yet reached [p = 0.13]). Consolidation patients had a longer median PFS (55.3 vs 34.4 months [p = 0.001]), but no significant gain in median OS (p = 0.065). Patients who received lenalidomide-based maintenance experienced a median PFS of 53.7 months and OS of 159 months. In the multivariable analysis, use of any type of maintenance therapy vs no maintenance was associated with a lower risk of progression (HR 0.52 (95% CI 0.47-0.57)) and death (HR 0.58 (95% CI 0.51-0.67)). This real-world study demonstrates that, overall, first-line treatment sequence in transplant-eligible patients produces a median OS of ≥10 years. It also highlights the contribution of post-ASCT maintenance, particularly lenalidomide given until progression.

Higher efficacy of Etoposide + Cytarabine Plus Pegfilgrastim in poorly mobilizing Multiple Myeloma and lymphoma Patients

Background aimsAn optimal strategy for mobilizing hematopoietic stem cells in poorly mobilizing patients with multiple myeloma (MM) and lymphoma has not yet been determined. MethodsWe retrospectively analyzed the efficacy and safety of etoposide combined with cytarabine (etoposide 75 mg/m2, daily d1∼2; Ara-C 300 mg/m2, every 12 h d1∼2), plus pegfilgrastim (6 mg d6) in 32 patients with MM or lymphoma, among whom 53.1% were defined as “proven poor mobilizers.” ResultsThis approach resulted in adequate mobilization (≥2.0 × 106 CD34+ cells/kg) in 93.8% of patients and optimal mobilization (≥5.0 × 106 CD34+ cells/kg) in 71.9% of patients. A total of 100% of patients with MM reached at least 5 × 106 CD34+ cells/kg collected, the amount required for double autologous stem cell transplant. In total, 88.2% of patients with lymphoma reached at least 2 × 106 CD34+ cells/kg collected, the amount required for a single autologous stem cell transplant. This was achieved with a single leukapheresis in 78.1% of cases. A median peak number of 42.0/μL circulating CD34+ cells and a median number of blood CD34+ cells counts in 6.7 × 106/L were collected among 30 successful mobilizers. Approximately 6.3% of patients required plerixafor rescue, which was successful. Nine (28.1%) of the 32 patients suffered grade 2∼3 infections, and 50% required platelet transfusions. ConclusionsWe conclude that chemo-mobilization with etoposide, Ara-C and pegfilgrastim in poorly mobilizing patients with MM or lymphoma is very effective and has acceptable toxicity.

Single or tandem autologous stem cell transplantation for treating Chinese patients with refractory/relapsed classical Hodgkin lymphoma.

Autologous stem cell transplantation (ASCT) is the standard treatment strategy for refractory or relapsed classical Hodgkin lymphoma (R/R cHL). However, a single transplantation is insufficient to cure the disease because of unfavorable risk factors. Herein, we evaluated the outcomes of single or tandem ASCT in patients with R/R cHL, especially in high-risk patients. We retrospectively analyzed R/R cHL patients who underwent single or tandem ASCT between April 2000 and June 2021 at the Beijing Cancer Hospital and Peking University International Hospital. A total of 134 patients were enrolled. Patients were allocated to a favorable-risk group (group A, n = 33), an unfavorable-risk group (group B, n = 81) that underwent single ASCT, and an unfavorable-risk group that underwent tandem ASCT (group C, n = 20). The median follow-up time was 99 months (range, 91-107 months), and no treatment-related deaths occurred after single or tandem ASCT. However, 27 patients (2 in group C) died during the follow-up period. The groups A, B, and C had 5-year progression-free survival (PFS) rates of 77.05%, 45%, and 74.67%, respectively (p = 0.0014), and 5-year overall survival (OS) rates of 89.85%, 76.06%, and 95%, respectively (p = 0.18). Neither the median PFS rates of groups A and C nor the OS rates of all groups were reached. Our study discusses the advantages of tandem transplantation for high-risk patients with R/R cHL.

Impact of autologous stem cell transplantation (ASCT) on progression free survival (PFS) in newly diagnosed multiple myeloma patients (NDMM) with high risk cytogenetic abnormalities.

ASCT has been considered the standard of care for younger patients with NDMM, however, not all the studies published so far have uniformly demonstrated the complete superiority of ASCT over chemotherapy at standard doses. A systematic review and meta-analysis of randomized studies has shown a significant benefit with single ASCT in terms of prolonged progression-free survival (PFS), but not of overall survival (OS). In our retrospective analysis we investigated the impact of high dose (HD) chemotherapy followed by ASCT in special population of patients with high risk cytogenetic profile on the PFS and treatment outcome. Retrospective analysis of NDMM patients eligible for HD chemotherapy followed by upfront ASCT in the era of novel agents, who underwent the ASCT in the Department of hematology and oncohematology LF UPJŠ and UNLP Košice in the timeframe of 54 months (from 01/JAN/2019 to 30/JUN/2023). Patients were stratified according to their cytogenetic profile. PFS was defined by the time from ASCT to the disease progression. The OS was defined as the time from the the start of treatment to the death from disease progression. The high risk cytogenetic abnormalities (HRCA) were defined as t(4;14), del(17/17p), t(14;16), t(14;20), nonhyperploidy, gain (1q). Inclusion criteria were met by 65 patients with NDMM who received HD chemotherpy followed by ASCT. We identified 22 (33.8 %) patients with HRCA and 43 (66.2 %) patients with standard cytogenetic risk. During the monitored period we recorded 4 deaths due to disease progression, all of them in the HCRA subgroup. The response was enhanced by the ASCT in both subgroups. The very good partial response (VGPR) increased from 42 % to 46 % and complete remission (CR) increased from 23 % to 45 % after the ASCT. The number of patients achieving only partial response (PR) decreased from 35 % to 9 % after ASCT. In the subgroup of patients with HRCA the median PFS after ASCT was lower compared to the patients with standard cytogenetic risk (17 vs 38 months). The average PFS in both subgroups was 22.9 months. The median OS in both subgroups was not reached, however the only deaths due to disease progression were recorded in the HRCA subgroup. At the time of analysis, 100 % (43) of patients are alive in the standard cytogenetic subgroup versus 72 % (18) of patients in HRCA subgroup. HD chemotherapy followed by ASCT remains the standard of care for NDMM eligible for high dose chemotherapy. Our results confirm the benefit of ASCT even in the presence of HRCA. Lower PFS in the HRCA subgroup might indicate the need for more intensive treatment, which may be achieved by tandem ASCT defined as two ASCT performed within a period of no more than six months. Additionally, as three- and four-drug induction therapies are becoming increasingly available and effective, resulting in high minimal residual disease (MRD) negative rates, it is important to continue discussing and further personalizing upfront ASCT to avoid overtreatment and possible toxicities especially in the non-high-risk patient population (Tab. 5, Fig. 2, Ref. 9).

Real-World Results of Autologous Stem Cell Transplantation in Newly Diagnosed Patients with Multiple Myeloma: A Multi-Institutional Report from the Canadian Myeloma Research Group (CMRG) Database

INTRODUCTION Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients (pts) as part of initial therapy. In Canada, fit younger pts are typically offered ASCT; selected centers offer tandem ASCT to high-risk (HR) pts; and current standard practice involves continuation of maintenance (maint) therapy until disease progression, which is facilitated by public funding for lenalidomide (len) in this setting. Using our national database, we examined the details and outcomes of ASCT performed as part of initial therapy in eligible Canadian MM pts. Methods The Canadian Myeloma Research Group database (CMRG-DB) contains both legacy and ongoing prospective data and can track and characterize real-world outcome of pts treated at 17 major Canadian institutions. All pts who received an ASCT as part of initial MM therapy between 01/Jan/2007 to 31/Dec/2021 were included. Progression-free survival (PFS) was calculated from the time of first ASCT until disease progression, death due to any cause or last follow up, whichever comes first, while overall survival (OS) was defined as the time from ASCT to the date of death or last follow up. Results 3821 pts underwent ASCT as frontline therapy and were included in the analysis. Median age was 61 (range 26-77) years, 15.2% had a creatinine > 177 umol/L and 18% had HR FISH [del17p, t(4;14) and t(14;16)] (FISH was unknown/missing in 50% of pts). The majority (82%) received bortezomib (btz)-based induction; this consisted of CyBorD in 72% with rates of ≥PR (≥VGPR) of 92% (60%). Only 1.6% received a proteasome inhibitor (PI) + len; rates of ≥PR (≥VGPR) were 96.5% (63.2%) in this subgroup. Median time to ASCT from start of induction was 5.6 months (mos). A second induction regimen, including len in 78.5%, was administered to 376 pts for suboptimal response/progression on first induction. The ≥PR (≥VGPR) rates in these 376 pts was 72.9% (35.4%) with a median time from start of second induction to ASCT of 4.2 mos. Tandem ASCT was performed in 314 pts, primarily in HR pts (64%). In HR FISH pts, the median PFS (mPFS) for single vs tandem ASCT was 25.1 vs 35.4 mos (p 0.018) and median OS (mOS) 91.5 vs 84.4 mos (p 0.048), respectively. For those without HR FISH, mPFS and mOS for single vs tandem ASCT were, respectively, 46.5 vs 33.8 mos (p <0.001) and 158.6 vs NYR (p <0.001). After ASCT, only 205 (5%) pts received consolidation that consisted of a PI + len in 93.2%. However, 2060 pts (53.9%) received post-ASCT maint (len +/- steroids in 63.1%, btz +/- steroids in 2.1 %, len + btz +/- steroids in 1.7%, other PI +/- steroids in 1.6%, len + other PI +/- steroids in 5.7 % and thalidomide +/- steroids in 8.5%). The mPFS and mOS for all pts was 35.4 mos (95% CI 33.7-37.3) and 125 mos (95% CI 120-138) from first ASCT. Table 1 summarizes the mPFS and mOS according to treatment. Those given a second induction regimen had significantly inferior outcomes (mPFS 27.9 vs 36.2 mos [p 0.001]; mOS 118 vs 126 mos [p 0.011]), although the use of maintenance led to comparable results regardless of number of induction regimens (mPFS 55.3 vs 51.1 mos [p 0.11]; mOS 158.6 vs not yet reached (NYR) [p 0.13]). Consolidation pts had a better mPFS (55.3 vs 34.4 mos [p 0.001]), but no significant gain in mOS (p 0.065). The mPFS and mOS were 48.8 vs 24.5 mos and 159 vs 105 mos for the maint vs non-maint cohorts, respectively, when all types of maint were included. For pts receiving len, btz or both (+/- steroids), the mPFS was 53.7 mos vs 48.2 mos vs 43.5 mos, respectively, while the mOS was 159 mos vs NYR vs 115 mos, respectively. Amongst pts receiving such maint, outcomes for pts with HR FISH were compared with those without HR FISH: mPFS was 36.6 mos vs 55.2 mos and the mOS was 97.4 mos vs 164.4 mos, respectively. CONCLUSIONS This large study demonstrates that the integration of btz and len into the transplant sequence produces a mOS of ≥10 yrs in most ASCT pts in the real-world setting. Our observations highlight the contribution of post-ASCT maint, particularly len given until progression, when used in multiple pt groups including those with and without HR, as well as those requiring a second induction regimen. Nevertheless, HR pts require additional strategies to optimize results. Further analyses to assess the relationship of pt characteristics, specific treatment details and outcomes are in progress. These results serve as Canadian benchmarks for comparison with newer approaches that combine immunotherapy with ASCT as initial therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Strategies to Optimize the Utilization of Stored Autologous Peripheral Blood Stem Cells for Second Transplantation in Multiple Myeloma

Introduction: Autologous stem cell transplantation (ASCT) is the standard of care and a mainstay in the management of eligible patients with multiple myeloma (MM) and remains relevant in the era of novel therapeutics. ASCT requires stem cell mobilization to collect ample stem cells to provide hematological recovery after myeloablative conditioning. Second ASCT (ASCT2) as salvage therapy in relapsed/refractory MM (RRMM) is a treatment option for patients who achieved disease control for 2 to 3 years after first ASCT (ASCT1). The reported difficulties in mobilizing and collecting additional stem cells following myeloablative ASCT1 have led to the currently adopted practice to collect and store adequate peripheral blood stem cells (PBSCs) for two transplants before ASCT. The preferred PBSC cell dose is 2 to 5 × 106 CD34+ cells per kilogram of recipient weight (CD34+ cells/kg) per transplant; however, with the influx of effective novel agents available for RRMM, the use of ASCT2 is declining. A retrospective cost utilization study showed that at a median follow-up of 3.5 years, only 3% of the cohort received ASCT2. The additional cost of collecting and storing these products is an average of 16,590 USD/patient. Given the limited use of salvage ASCT2, current practice of collecting PBSCs for two transplants should be re-evaluated and carefully selected case-by-case. We investigated potential strategies to reduce the financial burden of PBSC collection, processing, and storage by identifying a subgroup of patients who are less likely to receive an ASCT2, herein avoiding storing extra cells. Materials and Methods: With Institutional Review Board approval, we performed a retrospective descriptive analysis of all MM patients who underwent frontline ASCT from 1/1/2012 to 6/23/2022. We excluded patients who had planned tandem transplants and those who underwent a single ASCT and had all cells infused with no remaining stored cells. We classified all patients who collected a sufficient cell dose for ASCT1 and ASCT2 into two cohorts according to the number of ASCT received; those who received ASCT1 and those who received ASCT1 and ASCT2. Results: We report the descriptive statistics of eligible MM patients from a single stem cell transplant center. Over a median follow-up of 2.0 years, we report findings of 240 patients who collected sufficient PBSCs for ASCT1 and ASCT2. Patients’ median age at PBSC collection was 61 (range 32-77). We classified our cohort by gender, age, race, and average number of days for PBSC collection. We aim to collect a cell dose of 10 x 106 CD34+ cells/kg. Our cohort included more males than females (132/108) and a higher prevalence of African Americans (59%) than Caucasians. Our study showed that only 7% of patients underwent ASCT2 (17/240) with average time between ASCT1 and ASCT2 of 2.9 years. We noticed that 88% (15/17) of patients who received ASCT1 and ASCT2 were ≤ 61 years old at the time of ASCT1 and two patients (12%) were ≥ 70 years. Additionally, a higher proportion of patients utilizing ASCT2 in the youngest age groups is noticeable. Six of 30 patients under 50 years and three of seven patients under 40 years of age (20% and 43%, respectively) underwent ASCT2. The data highlights that utilization of ASCT2 is less common in the elderly population; hence considering PBSC collection for one transplant among the elderly would be a cost-effective strategy. Most stem cell transplant centers inherited a strategy to collect PBSC 10 x 106 CD34+ cells/kg. We noticed that 102 patients required >1 day of PBSC collection to meet the collection goal. Of these patients, 35% were age 65 or older. If we were to change practice and consider PBSC collection for one transplant among the elderly, we could have reduced the number of collection days by 25 and reduced the associated costs of collection, processing, storage, and staffing, as well as space requirements for storage. Conclusion: The utilization of ASCT2 in MM patients is decreasing with the influx of novel therapeutics. Potential strategies are needed to change the practice and reduce the additional financial burden of excess stem cell collection and storage. We suggest that elderly MM patients be considered for PBSC collections for a single transplant. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Stem Cell Mobilization Characteristics for Transplant Eligible Patients with Newly Diagnosed Multiple Myeloma (NDMM) Treated with Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab (KRd-Dara)

Introduction: CD38 monoclonal antibody (mAb)-containing quadruplet regimens have been shown to improve depth and duration of response in patients with NDMM eligible for autologous stem cell transplant (ASCT). However, some studies have raised concerns about the detrimental effect of combined lenalidomide and CD38 mAbs on stem cell mobilization. As an exploratory endpoint, we evaluated the effect of KRd-Dara on stem cell mobilization and collection in the Levine Cancer Institute (LCI) KRd-Dara study (NCT04113018) that permits up to 8 cycles of induction with KRd-Dara followed by an MRD-directed treatment algorithm for transplant-eligible and transplant-noneligible patients (Bhutani et al, Blood 2020 Abstr 1388). We provide a table summarizing our results from stage 1, along with two other phase II studies, the MANHATTAN (Landgren et al, JAMA Oncol 2021) and the MASTER (Costa et al, JCO 2021) studies that used variable numbers of KRd-Dara induction cycles prior to stem cell apheresis. Patients and study design: Eligible patients had NDMM and an ECOG performance status score of 0-2. Induction treatment consisted of 28-day cycles of KRd-Dara with intravenous carfilzomib, 20/56 mg/m2 (days 1, 8, and 15); lenalidomide orally, 25 mg (days 1-21); dexamethasone weekly; daratumumab (subcutaneous) per standard approved dosing schedule. One pre-study cycle with non-protocol therapy was allowed. During stage I of the study, stem cell collection for transplant-eligible patients was performed after 8 cycles of induction. All patients were mobilized with granulocyte-colony stimulating factor (G-CSF, 10 µg/kg) daily for 5 days. Preemptive Plerixafor was administered in the evening of Day 4 if the blood CD34+ cell count was <50/µl. Collection was done over 2 days in some patients who failed to collect sufficient CD34+ cells during the first day. A second mobilization attempt after a few weeks of additional wash-out was allowed. Our center-specific minimum required collection target is 3 x 106 CD34+ cells/kg, below which the stem cell dose is considered inadequate to perform a single ASCT. Physicians requested collection for potentially 2 or 3 transplants per patient, with a collection goal of 8 -12 x 106 CD34+ cells/kg. Mobilization failure was defined as the proportion of patients with Day 4 CD34 count <1/µl or collection of <3 x 106 CD34+ cells/kg (considered inadequate for even one ASCT) during the first mobilization attempt. Results: Among the 22 mobilized patients during stage 1 analysis, the median age was 60 years (range, 34 to 72) and 32% were African Americans. Eighteen patients received plerixafor, 3 did not based on futility as their Day 4 blood CD34 count was zero, and only one patient met the threshold of not receiving Plerixafor. The median total CD34+ cells collected were 7.73 x 106/kg (range, 0.00-19.18). Six (27%) patients had mobilization failure after their first attempt. Four of these patients underwent a second attempt after a median of 56 days (range, 36-98 days), with only one patient collecting enough CD34+ cells for one ASCT. Of the 10 patients whose collection goal was 2 transplants (8 million CD34 cells/kg), 9 patients did not meet the goal. Of the 12 patients whose collection goal was 3 transplants (12 million CD34 cells/kg), 8 patients did not meet the goal. Conclusions: The stem cell mobilization failure rate was high in patients collecting after 7 or 8 cycles KRd-Dara. Second remobilization with G-CSF and plerixafor was successful in only 1 of the 4 patients. We have modified stage 2 of the protocol to allow stem cell collection after cycle 3 of KRd-Dara induction. We plan to do combined analyses of LCI, MANHATTAN and MASTER to determine predictive factors associated with poor stem cell mobilization after KRd-Dara induction. Based on our results, we recommend stem cell collection after 3-4 cycles of KRd-Dara regimen. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long-Term Outcomes in Patients with Plasma Cell Myeloma Following High-Dose Chemotherapy with Autologous Stem Cell Transplantation

Plasma cell myeloma (PCM) is a hematopoietic malignancy characterized by the neoplastic proliferation of clonal plasma cells in the bone marrow. High-dose chemotherapy (HDCTx) followed by autologous stem cell transplantation (ASCT) is considered the standard of care treatment for eligible patients. Although the introduction of new therapeutic agents has further contributed to improved survival outcomes, the disease remains incurable, with most patients eventually experiencing relapse or disease progression. Circulating tumor cells at the time of stem cell collection that are reinfused with the autograft may be one of the factors influencing the clinical outcomes. The objective of this study was to evaluate the association of patient- and treatment-related parameters with progression-free survival (PFS) and overall survival (OS) in PCM patients who underwent ASCT. The survival data of 204 patients diagnosed with PCM who received ASCT between 2010 and 2014 at the University Hospital Zurich were collected and analyzed. Most patients received proteasome inhibitor- or immunomodulatory drug-based induction therapy followed by high-dose melphalan conditioning before ASCT. The median PFS was 33.3 months and the median OS was 65.1 months. In patients with follow-up data of at least 5 years (n=174), the estimated 5-year OS rate was 68.4%. The median number of reinfused CD34^+^ cells was 3.77x10^6^ per kg body weight per reinfusion. In patients who received single ASCT (n=144), no significant difference was observed based on the mean number of reinfused CD34^+^ cells (three tiers: <2.65x10^6^ vs 2.66−4.49x10^6^ vs >4.49x10^6^ CD34+ cells per kg body weight per reinfusion) in terms of OS (p=0.103) and PFS (p=0.704). There was also no significant difference in OS (p=0.786) and PFS (p=0.425) correlated with remission status on the day of ASCT. In conclusion, this study suggests that the anticipated influences of graft composition no longer play a major role in the era of modern second- and subsequent lines of therapies. HDC and ASCT remain the mainstay of therapy for eligible patients and further investigations into variables influencing the outcome of PCM patients are warranted.

MM-531 Case Control Study of Outcomes of Autologous Stem Cell Transplantation in Jehovah's Witness Multiple Myeloma Patients

Jehovah's Witnesses (JW) persons do not accept blood transfusions. Autologous stem cell transplantation (ASCT) after using high-dose chemotherapy is the standard of care in treatment of multiple myeloma (MM). Patients usually require blood transfusions during ASCT. We sought to analyze safety outcomes of single or tandem ASCT in JW MM patients. We performed a case control study at the University of Arkansas for Medical Sciences for JW and non-JW MM patients who underwent single or tandem ASCT from 1990-2021. Matching (1:2) was done based on age, date of MM diagnosis, race/ethnicity, performance status, stage indicated by International Staging System (ISS), and number of ASCT. Wilcoxon Rank-Sum test was used to test continuous variables, while Fisher's exact test was used for categorical variables. A total of 13 JW MM patients received ASCT in the study period (8 single, 5 tandem) compared to 26 non-JW MM patients (16 single, 10 tandem). For JW patients who received single ASCT, median age was 66 (range:65.8-67.5 years), 50% were female, 62.5% were black. Average CD34 stem cells collected/infused were 23/5.8 million cells in JW compared to 30.1/5.1 million cells in non-JW, respectively. For JW patients who received tandem ASCT, median age was 49 (range:46-52 years), 50% were female, 62.5% were black. Average CD34 stem cells collected/infused were 34/10.8 million in JW compared to 21.3/8.8 million in non-JW, respectively. Lowest hemoglobin and platelets level in JW were 6.6 g/dl and 3000 k/uL, respectively. 100-days mortality for all patients was 0%. Multivariable analysis showed no significant difference in 30 days/100 days re-hospitalization, major and/or minor bleeding adverse events, response to treatment (very good partial response or better). Bloodless single/tandem ASCT can be done safely for selected JW MM patients with no significant difference in safety/outcomes.

S175: ATLAS: A PHASE 3 RANDOMIZED TRIAL OF CARFILZOMIB, LENALIDOMIDE, AND DEXAMETHASONE VERSUS LENALIDOMIDE ALONE AFTER STEM-CELL TRANSPLANT FOR MULTIPLE MYELOMA

Background: Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), suggesting a benefit of post-ASCT KRd therapy. Aims: We report the results of ATLAS, a multicenter, international, open-label randomized phase 3 study to determine the efficacy and safety of post-ASCT KRD vs standard lenalidomide (R) maintenance (NCT02659293). Methods: Newly-diagnosed MM patients (pts) who received any induction therapy for up to 12 months (mo) followed by single ASCT and achieved at least stable disease within 100 days afterward were randomized to receive either KRd or R, stratified by post-transplant response (≥VGPR vs <VGPR) and cytogenetic risk [standard risk (SR) vs high [HR: presence of t(4;14), t(14;16), or del(17p)]. Pts randomized to KRd received carfilzomib 36 mg/m2 on days (D) 1,2,8,9,15,16 for 4 cycles (C) then D1,2,15,16 starting C5; R 25 mg D1-21, and dexamethasone 20 mg D1,8,15,22 in 28-day cycles. KRd pts with SR who reached IMWG-defined MRD-negativity after C6 de-escalated therapy to R alone after C8 (KRd->R); the rest continued KRd through C36 followed by R alone until progression. Pts randomized to R received lenalidomide 10 mg C1-3 and then 15 mg daily. The primary endpoint was progression free survival (PFS) rate: based on historical PFS rates, a sample size of 180 Pts was calculated to provide 85% power with 2-sided alpha 0.05. Secondary endpoints included minimum residual disease (MRD) negativity response rates and treatment-related adverse events. Results: 180 pts were enrolled (R n=87; KRd n=93) through 10/21/20; data cutoff was 12/31/21. Pt characteristics in the KRd and R arms were balanced for median age (58 vs 59 yrs), ≥VGPR (88% vs 92%), and HR (23% vs 21%). After 6 cycles, 47% pts in the KRd arm and 29% in the R arm achieved MRD-negativity (p=0.017). 34 KRd pts eligible for de-escalation converted to R alone after C8 and were analyzed on the KRd arm per intention-to-treat. At median follow-up of 33.8 mo, 23 pts (25%) on the KRd arm and 38 pts (44%) on the R arm progressed; estimated median PFS was 59.0 mo for KRd vs 41.4 mo for R (Hazard Ratio 0.56, logrank p=0.026). At cutoff, 90% of KRd and 87% of R pts were alive; no deaths were treatment-related. All-grade toxicities were generally comparable between arms. The most common grade 3+ AEs and those of special interest were neutropenia (KRd 47%; R 59%), thrombocytopenia (KRd 13%; R 7%), infections (KRd 15%; R 6%), cardiovascular toxicities (KRd 4%, R 5%), and secondary malignancies (KRd 2, R 2). Image:Summary/Conclusion: This is the first randomized phase 3 trial demonstrating superior PFS with extended post-transplant KRd therapy compared to R maintenance. Therefore, MRD/risk-adapted post-ASCT extended KRd treatment may represent a new standard of care.

ATLAS: A phase 3 randomized trial of carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma.

8001 Background: Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), suggesting a benefit of post-ASCT KRd therapy. Here we directly compare that strategy to standard lenalidomide (R) maintenance. Methods: This international open-label phase 3 randomized trial recruited newly-diagnosed MM patients (pts) who received any induction therapy for up to 12 months (mo) followed by single ASCT and achievement of at least stable disease within 100 days afterward. Pts were randomized to receive either KRd or R, stratified by post-transplant response (≥VGPR vs &lt; VGPR) and cytogenetic risk [standard risk (SR) vs high [HR: presence of t(4;14), t(14;16), or del(17p)]. Pts randomized to KRd received carfilzomib 36 mg/m2 on days (D) 1,2,8,9,15,16 for 4 cycles (C) then D1,2,15,16 starting C5; R 25 mg D1-21, and dexamethasone 20 mg D1,8,15,22 in 28-day cycles. KRd pts with SR who reached IMWG-defined MRD-negativity after C6 de-escalated therapy to R alone after C8 (KRd- &gt; R); the rest continued KRd through C36 followed by R alone until progression. Pts randomized to R received lenalidomide 10 mg C1-3 and then 15 mg daily. The primary objective was to compare progression free survival (PFS) rate between the two arms. Based on historical PFS rates, a sample size of 180 Pts was calculated to provide 85% power with 2-sided alpha 0.05. Results: 180 pts were enrolled (R n = 87; KRd n = 93) through 10/21/20; data cutoff was 12/31/21. Pt characteristics in the KRd and R arms were balanced for median age (58 vs 59 yrs), &gt;VGPR (88% vs 92%), and HR (23% vs 21%). After 6 cycles, 47% pts in the KRd arm and 29% in the R arm achieved MRD-negativity (p = 0.017). 34 KRd pts eligible for de-escalation converted to R alone after C8 and were analyzed on the KRd arm per intention-to-treat. At median follow-up of 33.8 mo, 23 pts (25%) on the KRd arm and 38 pts (44%) on the R arm progressed; estimated median PFS was 59.0 mo for KRd vs 41.4 mo for R (Hazard Ratio 0.56, logrank p = 0.026). At cutoff, 90% of KRd and 87% of R pts were alive; no deaths were treatment-related. All-grade toxicities were generally comparable between arms. The most common grade 3+ AEs and those of special interest were neutropenia (KRd 47%; R 59%), thrombocytopenia (KRd 13%; R 7%), infections (KRd 15%; R 6%), cardiovascular toxicities (KRd 4%, R 5%), and secondary malignancies (KRd 2, R 2). Conclusions: This is the first randomized phase 3 trial demonstrating superior PFS with extended post-transplant KRd therapy compared to R maintenance. Therefore, MRD/risk-adapted post-ASCT extended KRd treatment may represent a new standard of care. Clinical trial information: NCT02659293.

Outcomes for transplant-eligible, newly diagnosed Black patients (Pts) with multiple myeloma (MM): The Levine Cancer Institute (LCI) experience.

8053 Background: Studies have revealed disparities for Black (B) pts with MM, including more advanced disease at presentation, delayed therapy with novel agents such as immunomodulatory drugs (IMIDs) and proteasome inhibitors (PIs), reduced access to autologous stem cell transplant (ASCT), and under-representation in clinical trials. However, B pts tend to be younger at diagnosis and less likely to harbor high risk disease biology, suggesting outcomes could be better relative to their White (W) counterparts. To better understand outcomes by race in the setting of more optimal treatment access, we pursued a retrospective analysis of pts treated at LCI undergoing ASCT as part of first line therapy. Methods: 255 pts (181 W pts, 74 B pts) transplanted between 3/2014 – 12/2018 were included. Analysis was restricted to pts with MM who underwent a single ASCT as part of first line therapy. Pts with &lt; 1 year of follow-up and no overall survival (OS) events were excluded. Proportions were compared between groups with Fisher’s exact tests; OS and progression free survival (PFS) were evaluated with Kaplan Meier methods and compared between groups with log-rank tests. Results: Median follow-up for B and W pts was 5.0 yrs (0.9 – 7.8 yrs) and 4.1 yrs (0.5 – 8.0 yrs). At initial presentation, median age was 59 yrs (24 – 76 yrs) and 61 yrs (35 – 78 yrs, P= 0.038), anemia was present in 81.3% and 64.6% ( P= 0.020), renal impairment in 41.3% and 33.1% ( P= 0.335), and high-risk cytogenetics [gain 1q21, t(4;14), t(14;16) or del(17p)] in 25.4% and 35.9% ( P= 0.162) of B and W pts, respectively. Median time from diagnosis to ASCT was 0.6 yrs (0.3 – 2.4 yrs) and 0.5 yrs (0.3 – 2.0 yrs) for B and W pts. 35.2% of all B pts and 43.9% of all W pts treated at LCI during the study period underwent ASCT (48.3% and 64.4% of pts ≤70 yrs of age, P= 0.002), while 63.5% and 80.1% received PI/IMID-based induction therapy ( P= 0.009) and 90.5% and 93.4% received maintenance therapy post-ASCT ( P= 0.438), respectively. Although ≥very good partial responses were achieved in fewer B pts than W pts after induction (65.8% and 80.7%,( P= 0.014), there was no difference after ASCT (95.8% and 93.9%, P= 0.759). Median PFS was 5.9 yrs (95% CI 3.4 – 6.6) and 3.6 yrs (95% CI 3.0 – 4.5) for B and W pts ( P= 0.039). Median OS trended in favor of B pts ( P= 0.163) with 5-year OS of 83.0% (95% CI 71.2% - 90.3%) and 74.2% (95% CI 65.8% - 80.9%), respectively. Conclusions: Despite disparities in optimal induction therapy, Black pts with MM who underwent frontline ASCT enjoyed better PFS relative to W pts. Optimizing access to PI/IMID-based induction therapy and ASCT will be necessary to further improve OS.

Long-Term Follow-Up of Multiple Myeloma Patients Treated with Tandem Autologous Transplantation Following Melphalan and Upon Recovery, Total Marrow Irradiation

Total body irradiation in combination with melphalan for multiple myeloma (MM) has been shown to be prohibitively toxic. To ameliorate toxicity, total marrow irradiation (TMI) has been administered as the sole ablative modality during the second cycle of tandem autologous stem cell transplantation (TASCT) for MM patients on a phase I-II trial. Patients with MM in response or with stable disease and ≤18 months from diagnosis received melphalan 200 mg/m2 and autologous stem cell transplantation (ASCT) (cycle 1) and then, after recovery, TMI and another ASCT (cycle 2), followed by maintenance with an immunomodulatory drug (ImiD) and dexamethasone for up to 12 months. TMI doses were escalated from 1000 cGy to 1800 cGy in 200-cGy increments. Fifty-four patients were to receive TASCT between 2004 and 2011; 8 patients received single ASCT because of patient or physician preference. The median time between melphalan and TMI was 65 days (range, 47 to 125 days). Thirty patients (55.6%) underwent TASCT at the maximum tolerated dose of 1600 cGy. The complete response and very good partial response rates were 48.1% and 22.2%, respectively, following ASCT and maintenance. The median follow-up among survivors was 12.3 years (range, 9.2 to 15.5+ years). Progression-free survival (PFS) and overall survival at 10 years were 20.4% (95% confidence interval [CI], 10.9% to 31.9%) and 38.8% (95% CI, 25.9% to 51.5%), respectively. Secondary neoplasms included (1 each) acute myelogenous leukemia, papillary thyroid and prostate carcinoma, and melanoma, and there was 1 case of ductal carcinoma in situ and 4 cases of nonmelanoma skin cancers. TMI as part of TASCT was well tolerated, and TASCT was associated with a 20.4% PFS plateau. The inclusion of TMI as a conditioning regiment for MM before ASCT warrants further study in the context of modern induction and maintenance therapies.

Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). The availability of techniques such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment allowed the design of MRD-based response-adjusted trials that will define, in particular, the role of consolidation and maintenance therapies. In this review, we will provide an overview of the most recent evidence and the future prospects of ASCT in MM patients.

High Efficacy of Stem Cell Mobilization With Etoposide+Cytarabine Plus G-CSF in Patients With Multiple Myeloma.

BackgroundEfficient mobilization of CD34+ hematopoietic stem cells plays a vital role in successful autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM), especially in cases with high-risk cytogenetic recommended for tandem ASCT. However, the optimal mobilization strategy remains a matter of debate in the era of lenalidomide. The combination of etoposide with Cytarabine plus G-CSF as a novel mobilization regimen in MM has not been reported previously.MethodsThis research retrospectively studied mobilization efficacy and safety using etoposide combined with Cytarabine (etoposide 50–100 mg/m2, qd d1–3; AraC 0.5 g/m2, q12h d1~3) plus G-CSF (5 µg/kg/day, from d5 until the day of apheresis) in 128 patients with MM. 70(54.7%) patients received lenalidomide-based induction regimens treatmentResultsA median of 27.75×106 CD34+ cells/kg was collected in the first apheresis, and 28.23×106 CD34+ cells/kg were collected overall. Of the 128 patients, all achieved adequate collection (≥2×106 CD34+ cells/kg), 121(94.5%) achieved optimal collection for single ASCT (≥5×106 CD34+ cells/kg), and 114(89.1%) harvested optimal collection for tandem ASCT (≥10×106 CD34+ cells/kg). In particular, the target yield of optimal collection for tandem ASCT was reached in 82.8% (106/128) by a single apheresis procedure. 14 patients obtained deeper response post mobilization. In multivariate analysis, cycles of prior chemotherapy independently affected the optimal achievement of CD34+ cells (p=0.004, OR 0.695, 95% CI 0.544~0.888). Previous lenalidomide exposure did not significantly impair CD34+ cells collection. Although 68% episodes of antibiotic usage were observed, no severe infection or treatment-related mortality occurred.ConclusionStem cell mobilization with Etoposide + Cytarabine plus G-CSF was highly efficient and safe in patients with MM, which could be considered in high-risk MM patients who were referred for tandem ASCT.

Salvage High-dose Melphalan With Autologous Stem cell Transplantation as Bridge to Consolidation Therapy for Chemoresistant Aggressive B-cell Lymphoma

BackgroundPatients suffering from refractory aggressive B-cell lymphoma not responding to salvage chemotherapy have a dismal prognosis. CAR T-cells or allogeneic stem cell transplantation (SCT) are potentially curative approaches. However, obtaining a remission, and lowering tumor burden before consolidation seems crucial for long-term efficacy of both treatment modalities. Materials and MethodsIn this retrospective analysis, we reviewed patients with chemoresistant aggressive B-cell lymphoma, defined as being refractory or progressive to at least second line salvage chemotherapy including the regimen immediately preceding autologous stem cell transplantation (ASCT), treated at 2 tertiary centers, who were eligible for intensive treatment using single agent high-dose (HD) melphalan to obtain a remission before consolidating therapy. ResultsWe identified 36 patients that received single agent HD melphalan and ASCT as remission induction followed by CAR T-cells or allogeneic stem cell transplantation (SCT). Thirteen of the evaluable patients (39.4%) achieved a partial remission and 9 patients (27.73%) a complete remission, resulting in an overall response rate (ORR) of 66.7%. High remission rates were seen across all subgroups including patients with primary refractory lymphoma (ORR 58.3%), uncontrolled disease and high tumor burden as indicated by increased LDH levels (ORR 66.7% for patients with elevated LDH above 2 times upper limit of norm). 22 patients proceeded to allogeneic SCT and 5 to CAR T-cell therapy. Treatment related mortality of ASCT was 5.5% (2 patients, both due to infections). Two-year overall survival of all patients was 15.8%, primarily due to a high non–relapse mortality (45.5%) of allogeneic SCT patients treated with myeloablative conditioning chemotherapy. ConclusionSingle agent HD melphalan produces high remission rates in patients with chemoresistant, uncontrolled aggressive B-cell lymphoma and provides a window of opportunity for consolidation therapy. MicroabstractPatient with refractory/relapsed aggressive B-cell lymphoma after salvage therapy are an unmet medical need because of their very poor prognosis. In our retrospective analysis of 36 patients we showed that single agent high-dose melphalan can achieve high response rates (ORR 66.7%) even in uncontrolled disease enabling consolidation therapy e.g. with allogeneic stem cell transplantation or CAR T-cell therapy.

Analysis of the efficacy of autologous peripheral blood stem cell transplantation in high-risk neuroblastoma.

Objective: This study aimed to analyze the efficacy of autologous peripheral blood stem cell transplantation for high-risk neuroblastoma in China.Methods: The data of 90 high-risk neuroblastoma patients treated with the CCCG-NB 2015 regimen were reviewed. The baseline clinicopathological characteristics and prognosis were analyzed and compared. In addition, the prognoses of tandem autologous stem cell transplantation and single autologous stem cell transplantation groups were compared.Results: The results of survival analysis showed that autologous peripheral blood stem cell transplantation based on this pretreatment regimen significantly improved the prognosis of children in the high-risk group. The 3-year event-free survival (EFS) and overall survival (OS) rates for the transplantation group and the nontransplantation group were 65.5% vs. 41.3% (p=0.023) and 77.1% vs. 57.9% (p=0.03), respectively. There was no difference in the distribution of baseline clinical case characteristics between the single transplantation group and the tandem transplantation group (p>0.05), and there was no significant difference in EFS and OS between the two groups (p>0.05).Conclusion: Based on this pretreatment programme, autologous peripheral blood stem cell transplantation is safe and tolerable and significantly improves the prognosis of children in the high-risk group. The value of tandem autologous stem cell transplantation is worthy of further discussion, which should consider various aspects such as the transplantation medication regimen and the patient's state.