Transplantation For Multiple Myeloma Research Articles

Induction prior to autologous haematopoietic cell transplantation in multiple myeloma.

Induction chemotherapy followed by autologous haematopoietic cell transplantation and post-transplant therapy (including maintenance therapy with or without prior consolidation) is still considered as the standard of care for newly diagnosed young and fit multiple myeloma patients. Over the last years, superiority of quadruplet regimens for induction was established, with the addition of an anti-CD38 monoclonal antibody to triplet regimen including a proteasome inhibitor, an IMiD (thalidomide or lenalidomide) or cyclophosphamide, and dexamethasone. Given quadruplet induction regimens are associated with deep response, including a high-rate of sustained measurable residual disease negativity in a significant proportion of patients, they are now recommended for induction chemotherapy when available.

Modest survival benefits of autologous stem cell transplantation in multiple myeloma with renal impairment: a critical appraisal of the pre-antibody era

The benefit of high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HDM-ASCT) for multiple myeloma (MM) patients with renal insufficiency (RI) is debated. A systematic review and meta-analysis were conducted to assess the safety and efficacy of HDM-ASCT in MM patients with RIs, and the findings were compared with real-world data. The study included 26 articles, 13 of which were pooled for meta-analysis. We compared three different types of MM patients with RI against MM patients with normal renal function (NRF). These patients were: MM patients with RI at the time of transplantation; MM patients with RI at the time of diagnosis; MM patients with RI at diagnosis but with NRF at transplantation. The meta-analysis indicated that MM patients with RIs conditioned with melphalan ≤ 140 mg/m2 followed by ASCT had transplant-related mortality rates comparable to those without RIs. The complete response rates post-ASCT were similar between MM patients with RIs and those with NRF. Although progression-free survival (PFS) was statistically similar between the groups, MM patients with RIs had significantly poorer overall survival (OS) than those with NRF. The real-world data supported these findings. With a reduced dose of melphalan, ASCT is safe and effective for MM patients with RI. MM patients with RI have similar complete response rates and PFS after ASCT compared to MM patients with NRF. The lower OS in MM patients with RI indicates the need for further research to improve OS in these patients.

Kidney transplantation in multiple myeloma in 2023: A short review.

Patients with multiple myeloma (MM) frequently present with kidney involvement, of which a non-negligible proportion will progress to end-stage kidney disease. Kidney transplantation (KT) is the preferred kidney replacement therapy for selected patients; however, there are still many uncertainties regarding its application in MM patients. The risk of hematological relapse and subsequent graft loss or patient death often leads nephrologists to deem these patients unfit for KT. As such, data on KT in MM patients are heterogeneous and originate from individual case reports and small case series. Although MM is still an incurable disease, the addition of newer drugs and autologous hematopoietic stem cell transplant (HSCT) in the standard of care has been increasing patients' overall survival in recent decades. Risk stratification using cytogenetic studies and minimal residual disease detection are helpful in assessing the risk of relapse in patients who attain a complete response after HSCT. The greatest challenges remain the correct identification of patients who will most probably benefit from KT from a survival perspective and the determination of how long relapse-free survival should be before the transplant is performed.

Efficacy and survival outcome of allogeneic stem-cell transplantation in multiple myeloma: meta-analysis in the recent 10 years.

Allogeneic hematopoietic cell transplantation (alloHCT) possessed direct cytotoxicity and graft-versus-multiple myeloma effect (GvMM). Growing trials have shown survival benefits of performing alloHCT in both newly diagnosed and relapsed MM. We aimed to provide a comprehensive analysis in the recent 10 years to verify the efficacy and survival outcome of alloHCT in MM patients. A total of 61 studies which provide data between 14/04/2013 and 14/04/2023 and a total of 15,294 data from MM patients who had undergone alloSCT were included in our study. The best response rates (CR, VGPR, PR) and survival outcomes (1-, 2-, 3-,5-, and 10-year OS, PFS, NRM) were assessed. We further conducted meta-analysis in the NDMM/frontline setting and RRMM/salvage setting independently. The pooled estimate CR, VGPR, and PR rates were 0.45, 0.21, and 0.24, respectively. The pooled estimates of 1-, 2-, 3-, 5-, and 10-year OS were 0.69, 0.57, 0.45, 0.45, and 0.36, respectively; the pooled estimates of 1-, 2-, 3-, 5-, and 10-year PFS were 0.47, 0.35, 0.24, 0.25, and 0.28, respectively; and the pooled estimates of 1-, 2-, 3-, 5-, and 10-year NRM were 0.16, 0.21, 0.16, 0.20, and 0.15, respectively. In the NDMM/upfront setting, the pooled estimate CR rate was 0.54, and those for 5-year OS, PFS, and NRM were 0.69, 0.40, and 0.11, respectively. In a relapsed setting, the pooled estimate CR rate was 0.31, and those for 5-year OS, PFS, and NRM were 0.24, 0.10, and 0.15, respectively. Our results showed constant OS, PFS, and NRM from the third year onwards till the 10th year, suggesting that alloSCT has sustained survival benefits. Good response rate and promising survival outcome were observed in the NDMM/ frontline setting. Although comparing with other treatments, alloSCT had a lower response rate and poorer short-term survival outcome, long-term follow-up could reveal survival benefits of alloSCT in MM patients.

Maintenance therapy after Autologous Stem Cell Transplantation in Multiple Myeloma – currents and perspectives

MM is non-curable cancer that arises from plasma cells and is the second most common type of blood cancer. Drug-refractory relapses are inevitable, making it essential to sustain long-lasting remissions as part of therapy. Lenalidomide maintenance until progression is a standard of care for transplant-eligible newly-diagnosed patients. However, poor outcomes of high-risk patients and the risk of secondary primary malignancies associated with maintenance underline the need for novel approaches. Significant changes in frontline treatment maintenance are expected, with the increasing importance of minimal residual disease monitoring and the development of novel drug combinations for maintenance. This article explores current standards and prospects for maintaining response after upfront in ASCT in MM.

Allogeneic stem cell transplantation in multiple myeloma: is there still a place?

The introduction of novel agents dramatically improved response and outcomes of multiple myeloma (MM) and led to a sharp decline in the use of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Thus, recent guidelines do not recommend anymore allo-HSCT as consolidation in the first-line treatment of newly diagnosed MM, even in high-risk patients. In a relapsed/refractory setting, allo-HSCT is not routinely recommended but should only be performed within clinical trials in young and high-risk patients. Nonetheless, allo-HSCT still represents a potential curative approach that has been used for decades in the treatment of MM and plasma cell neoplasms with favorable results and may still represent a treatment option for carefully selected patients. Despite that promising results were obtained with CAR T-cell therapies and bispecific antibodies in triple- and penta-exposed/refractory MM, these patients will inevitably relapse. To date, less is known about outcomes of allo-HSCT in patients exposed to novel immunotherapeutic drugs. Therefore, allo-HSCT could represent a reasonable treatment choice for younger and high-risk patients who have relapsed after CAR T-cell therapies and bispecific antibodies as well as an alternative for patients not eligible to these treatments and in those countries where immunotherapies are not yet available. In the choice of conditioning, reduced intensity conditioning regimens are currently recommended for the lower toxicity and mortality. Moreover, the use of alternative donors, particularly haploidentical, has progressively increased in last years with results comparable to full matched donors. Finally, post-transplantation maintenance strategies are encouraged whenever feasible.

Cost effective utilization of apheresis for stem cell transplantation in multiple myeloma.

e19528 Background: Salvage autologous stem cell transplantation (ASCT) is an effective and feasible treatment option for patients with relapsed multiple myeloma (MM). It is standard practice to collect stem cells adequate for two transplants for ASCT eligible patients with newly diagnosed MM (NDMM). Stem cell collection is an expensive procedure due to the cost of granulocyte-colony stimulating factor, plerixafor, apheresis, chemotherapy in select cases and finally cryopreservation. However, the rate of utilization of second ASCT is not known. Methods: We conducted a single institution, retrospective study of 511 consecutive patients with NDMM who underwent ASCT to identify the proportion of patients receiving second ASCT. Patients received ASCT as front-line therapy between 1/1/2015-2/13/2019. Demographic and disease characteristics were summarized using median and range for continuous variables, and frequency and percentages were calculated for categorical variables. The cumulative incidence of second ASCT was estimated using the Fine and Gray method, and competing risk regression models were used to estimate the hazard ratios for risk of second ASCT. All statistical tests were two-sided with a type 1 error of < 0.05 indicating statistical significance. All estimates were reported with 95% confidence intervals (95% CI). Results: At a median follow-up of 4.7 years, 25 out of 511 patients received a second ASCT. The cumulative incidence rate at 5 years was 2.6% (95% CI 1.4-4.4%).Age at diagnosis, age at first ASCT and Charlson comorbidity index (CMI) were significantly associated with the risk of second ASCT in univariable analysis (UVA). In multivariable analysis (MVA) age at first ASCT was the only factor that was predictive of a second ASCT. We devised a predictive score for utilization of second ASCT using hazard ratios for each of the three significant factors noted in the UVA. Scoring was done as follows: age < 65 years – 1 point, > 65 years – 7 points; 1 point for CMI 0-1, 2 points for CMI 2 or higher; serum creatinine ≤1.2 – 1 point, > 1.2 – 3 points. Based on the total score, patients are grouped into low ( < = 3), medium (4-6) and high (7+) likelihood categories, with cumulative incidence rates of receiving second ASCT at 4.0% (95% CI: 1.3-9.1%), 3.4% (95% CI 1.4-7.0%) and 0.6% (95% CI 0.1-3.1%) respectively. Patients older than 65 years were 87% less likely to receive a second ASCT compared with those younger than 65 years (HR = 0.13, 95% CI 0.02-0.98). Conclusions: Using this predictive score, goal of stem cell collection for patients with MM could be determined more efficiently. This could avoid extra days of apheresis, chemo mobilization, hospitalizations and need for cryopreservation at least for patients with a low likelihood of second ASCT, translating into cost effective utilization of resources. We plan to validate this score prospectively in a larger group of patients with NDMM undergoing ASCT in the future.

Optimizing Autologous Stem Cell Transplantation in Multiple Myeloma: The Impact of Intensive Chemomobilization

Most transplant-eligible multiple myeloma (MM) patients undergo autologous peripheral blood stem cell collection (PBSC) using G-CSF with on-demand plerixafor (G ± P). Chemomobilization (CM) can be used as a salvage regimen after G ± P failure or for debulking residual tumor burden ahead of autologous peripheral blood stem cell transplantation (ASCT). Prior studies utilizing cyclophosphamide-based CM have not shown long-term benefits. At our center, intensive CM (ICM) using a PACE- or HyperCVAD-based regimen has been used to mitigate "excessive" residual disease based on plasma cell (PC) burden or MM-related biomarkers. Given the lack of efficacy of non-ICM, we sought to determine the impact of ICM on event-free survival (EFS), defined as death, progressive disease, or unplanned treatment escalation. We performed a retrospective study of newly diagnosed MM patients who collected autologous PBSCs with the intent to proceed immediately to ASCT at our center between 7/2020 and 2/2023. Patients were excluded if they underwent a tandem autologous or sequential autologous-allogeneic transplant, had primary PC leukemia, received non-ICM treatment (i.e., cyclophosphamide and/or etoposide), or had previously failed G ± P mobilization. To appropriately evaluate the impact of ICM among those who potentially could have received it, we utilized a propensity score matching (PSM) approach whereby ICM patients were compared to a cohort of non-CM patients matched on pre-ASCT factors most strongly associated with the receipt of ICM. Of 451 patients identified, 61 (13.5%) received ICM (PACE-based, n = 45; hyper-CVAD-based, n = 16). Post-ICM/pre-ASCT, 11 patients (18%) required admission for neutropenic fever and/or infection. Among 51 evaluable patients, the overall response rate was 31%; however, 46 of 55 evaluable patients (84%) saw a reduction in M-spike and/or involved free light chains. Among those evaluated with longitudinal peripheral blood flow cytometry (n = 8), 5 patients (63%) cleared circulating blood PCs post-ICM. Compared to patients mobilized with non-CM, ICM patients collected a slightly greater median number of CD34+ cells (10.8 versus 10.2 × 10⁶/kg, P = .018). The median follow-up was 30.6 months post-ASCT. In a PSM multivariable analysis, ICM was associated with significantly improved EFS (hazard ratio [HR] 0.30, 95% CI 0.14 to 0.67, P = .003), but not improved OS (HR 0.38, 95% CI 0.10 to 1.44, P = .2). ICM was associated with longer post-ASCT inpatient duration (+4.1 days, 95% CI, 2.4 to 5.8, P < .001), more febrile days (+0.96 days, 95% CI 0.50 to 1.4, P < .001), impaired platelet engraftment (HR 0.23, 95% CI 0.06 to 0.87, P = .031), more bacteremia (OR 3.41, 95% CI 1.20 to 9.31, P = .018), and increased antibiotic usage (cefepime: +2.3 doses, 95% CI 0.39 to 4.1, P = .018; vancomycin: +1.0 doses, 95% CI 0.23 to 1.8, P = .012). ICM was independently associated with improved EFS in a matched analysis involving MM patients with excessive disease burden at pre-ASCT workup. This benefit came at the cost of longer inpatient duration, more febrile days, greater incidence of bacteremia, and increased antibiotic usage in the immediate post-ASCT setting. Our findings suggest that ICM could be considered for a subset of MM patients, but its use must be weighed carefully against additional toxicity.

Prior Daratumumab Exposure and It's Correlation to Parameters Related to Apheresis Prior to Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Prior Daratumumab Exposure and It's Correlation to Parameters Related to Apheresis Prior to Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Significance of IgH Gene Rearrangement in Surveillance of Minimal Residual Disease after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

To investigate the value of immunoglobulin heavy chain (IgH) gene rearrangement in monitoring minimal residual disease (MRD) in multiple myeloma (MM) received autologous hematopoietic stem cell transplantation(auto-HSCT). The clinical data of 26 MM patients who received auto-HSCT in the Department of Hematology, Wuhan First Hospital from 2018 to 2022 were collected. IgH rearrangement was detected by multiplex PCR combined with capillary electrophoresis fragment analysis to evaluate minimal residual disease (MRD), and the outcome of the disease was analyzed statistically. Among the 26 MM patients, 18 were males and 8 were females, with a median age of 59(41-70) years. The median follow-up time after transplantation was 33 (7-52) months. Compared with the IgH rearrangement negative group (n=17), the proportion of CR and sCR of patients with IgH rearrangement positive in bone marrow samples before auto-HSCT at 3 months after transplantation was lower （1/9 vs 14/17）, and the duration of remission (DOR) after transplantation was shorter（10.78±4.35 vs 15.88±5.22 months）, with statistically significant difference in DOR between the two groups(P < 0.05). Compared with IgH rearrangement negative group (n=21), the proportion of CR and sCR of patients with positive IgH rearrangement results from peripheral blood stem cell collection at 3 months after transplantation was lower（0/5 vs 15/21）, the duration of remission (DOR) after transplantation was shorter（9.60±4.83 vs 15.19±5.11 months）, and the difference in DOR between the two groups was statistically significant (P < 0.05). During the follow-up period, 5 patients (5/9) with positive IgH rearrangement results in bone marrow specimens died, and all patients with negative IgH rearrangement results survived. Four patients (4/5) with positive IgH rearrangement results by peripheral blood stem cell samples died, while one patient (1/21) with negative IgH rearrangement results died. In both bone marrow and peripheral blood stem cell samples, the survival time of IgH rearrangement-positive patients after transplantation was shorter than that of IgH rearrangement-negative patients(P < 0.05). Logistic regression analysis showed that gender, disease stage, the proportion of bone marrow smear plasma cells at initial diagnosis, stem cell mobilization plan, efficacy evaluation before transplantation (≥CR and <CR), and CD34+ cell count had no effect on IgH rearrangement results of stem cell collection (P >0.05). By detecting IgH rearrangement of MM patients receiving auto-HSCT, the depth of MRD can be further evaluated, which has a certain guiding significance for the efficacy and prognosis of the disease.

Resource Utilization Analysis of Two Mobilization Regimens for Autologous Hematopoietic Cell Transplant in Multiple Myeloma

Resource Utilization Analysis of Two Mobilization Regimens for Autologous Hematopoietic Cell Transplant in Multiple Myeloma

T-cell redirection therapy after allogeneic stem cell transplantation in multiple myeloma: When the cure fails!

Allogeneic stem cell transplant remains an option for patients with myeloma. Given the unfortunate inevitability of the majority of patients, relapsing salvage therapy options are needed. Although there is a potential concern for subsequent T-cell redirection therapy in these patients, Hammons etal. provide a retrospective look at patients treated this way with no new significant adverse safety or efficacy signal. Commentary on: Hammons etal. Chimeric antigen receptor and bispecific T-cell engager therapies in multiple myeloma patients with prior allogeneic transplantation. Br J Haematol 2024;204:887-891.

Allogeneic Stem Cell Transplantation in Multiple Myeloma: Risk Factors and Outcomes in the Era of New Therapeutic Options-A Single-Center Experience.

Despite major treatment advances, multiple myeloma remains incurable. The outcome of patients who are refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies is poor, and improved treatment strategies for this difficult-to-treat patient population are an unmet medical need. This retrospective, unicentric analysis included 38 patients with relapsed/refractory multiple myeloma or plasma cell leukemia who underwent allogeneic stem cell transplantation (allo-HSCT) between 2013 and 2022. Survival outcomes, relapse incidence, and non-relapse mortality were calculated according to remission status, date of allo-HSCT, cytogenetic risk status, timing, and number of previous autologous HSCTs. The median PFS was 13.6 months (95% CI, 7.7-30.4) and the median OS was 51.4 months (95% CI, 23.5-NA) in the overall cohort. The cumulative incidence of relapse at 3 years was 57%, and non-relapse mortality was 16%. The median PFS and OS were significantly longer in patients with very good partial remission (VGPR) or better compared to patients with less than VGPR at the time of allo-HSCT (mPFS 29.7 months (95% CI, 13.7-NA) vs. 6.5 months (95% CI, 2.6-17.0); p = 0.009 and mOS not reached vs. 18.6 months (95% CI, 7.0-NA); p = 0.006). For selected patients, allo-HSCT may result in favorable overall survival, in part by providing an appropriate hemato-immunological basis for subsequent therapies.

A Conditioning Regimen of Bendamustine and Melphalan for Autologous Stem Cell Transplantation in Multiple Myeloma: A Phase 2, Single-Arm, Prospective Study

Aim: A registered study to investigate the efficacy and safety of bendamustine plus melphalan conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) (ChiCTR2100047782). Method: Bendamustine and melphalan were given to patients at the dose of 150 mg/m 2 on Days -5 and -4 and 70 mg/m 2 on Days -3 and -2, respectively. Progression-free survival (PFS) and overall survival (OS) were used to assess the efficacy and adverse events were used to assess the safety of the conditioning regimen. Results: A total of 80 patients were included in our study. Of them, 45 patients achieved complete response (CR); 7 patients achieved very good partial response (VGPR), and 28 patients achieved partial response (PR) before ASCT. With a median follow-up period of 16 months, the overall PFS rate was 91%, and the overall OS rate was 95%. Patients with CR pre-transplantation were all in CR until the last follow-up; two patients with VGPR pre-transplantation relapsed and one of them died; four patients with PR pre-transplantation relapsed and one of them died. The median time to neutrophile and platelet engraftment were 11 (9-13) and 13 (10-18) days. Three patients experienced sepsis during ASCT. Vomiting occurred in 45 (57.2%) patients; diarrhea occurred in 27 (34.2%) patients, transaminase elevation was observed in 18 (22.3%) patients; mucositis was found in 16 (18.8%) patients. All these adverse events were grade 1-2, and no grade 3-4 adverse events were observed. Conclusion: Bendamustine plus melphalan regimen is promising for ASCT in MM patients, and the long-term efficacy and safety remain to be investigated.

Prior Daratumumab Exposure and It's Correlation to Parameters Related to Apheresis Prior to Hematopoietic Stem Cell Transplantation in Multiple Myeloma

A number of recent studies have brought to light the potential detrimental effect the biologic monoclonal antibody daratumumab, directed towards CD38, may have on the collection of stem cell collection for hematopoietic stem cell transplantation (HSCT). In our evaluation of this claim, we retrospectively reviewed multiple myeloma patients who underwent autologous HSCT at a major tertiary transplant center between 2017 and 2022. A total of 240 patients were identified which included 62 patients who received daratumumab prior to stem cell collection and 178 patients who had no prior daratumumab exposure. Basic demographic data was collected as well as radiation, chemotherapy, and smoking history. No significant differences were identified between the groups based on demographics, smoking, or radiation exposure. Parameters related to peripheral stem cell collection were identified and recorded. We found that in patients exposed to daratumumab prior to apheresis, the mean number of days of apheresis required to reach the target collection goal was statistically increased compared to control (1.42 days ± 0.07 vs 1.26 ± 0.03; p&amp;lt;0.05). Furthermore, medications used to increase peripheral stem cell collection yield were also increased. It was demonstrated that the mean number of doses of plerixafor and G-CSF analogs were increased in the daratumumab group vs the control (1.08 ± 0.12 vs 0.6 ± 0.05; p&amp;lt;0.001 and 5.98 ± 0.31 vs 5.17 ± 0.06; p &amp;lt;0.001 respectively). Total number of stem cells collected both as an absolute number and controlled for the number of days of apheresis were lower in the daratumumab group compared to the control (5.31x10^6 ± 0.31 vs 6.68x10^6 ± 0.20; p&amp;lt;0.05 and 4.16x10^6 ± 0.32 vs 5.84x10^6 ± 0.21; p &amp;lt; 0.001 respectively). These results suggest that pre-apheresis exposure to daratumumab has a detrimental effect on peripheral stem cell collection. These results have a significant implications for both long term patient care and healthcare system resource utilization. The clinical outcome implications of daratumumab are currently not well known and further study is needed to determine if alterations in stem cell collection protocols would result in improved stem cell collection yields for patients with pre-collection daratumumab exposure. All data is expressed as mean ± SEM

Efficacy and Safety of Single Versus Tandem Autologous Stem Cell Transplantation in Multiple Myeloma: A Single-Center Retrospective Analysis in China

Background: Currently, there is a lack of comparative data on the efficacy and safety of single or tandem ASCT in China. This study aimed to review the efficacy and safety of single or tandem ASCT in MM patients without selection criteria for specific studies. Methods: Utilizing matched case-control study, we retrospectively analyzed the clinical data of 80 newly diagnosed MM (NDMM) patients who underwent ASCT in our department between November 2014 and June 2021, with 40 patients in each group receiving either single or tandem ASCT. Results: In single ASCT group, the percentage of ≥CR before or post ASCT was 50% and 70%, respectively. In tandem ASCT group, the percentage of ≥CR pre ASCT was 47.5%, while the percentage of ≥CR after 1 st and 2 nd ASCT was 65% and 85%, respectively. From 1 st transplantation, the median progression-free survival (PFS) was 33.2 and 71.1 months for the single and tandem arm, respectively (P=0.0099), and the median overall survival (OS) for the single and tandem arm was 38.3 and 75.8 months, respectively (P=0.0519). In the single and tandem group, 7-year PFS was 29.9% and 57.0%, while 7-year OS was 26.3% and 43.5%, respectively. The median PFS was 23.2 and 61.2 months for the single and tandem arm in patients with high risk (P=0.038), while the median OS was 32.4 months and 65.8 months, respectively (P=0.045). No transplant-related mortality occurred in both cohorts. The median times to neutrophil and platelet engraftment for single group were 11 days and 13 days, respectively. In the tandem group, the median times to neutrophil engraftment post 1 st and 2 nd transplantations were 11 days and 12 days, respectively, while the mean engraftment times for platelets were 12 days and 17 days. Mucositis, engraftment syndrome, and infection were common but manageable complications. Conclusion: Upfront tandem ASCT could deepen the depth of response and prolong PFS in MM patients and could be performed feasibly and safely in patients with myeloma, especially when novel agents are not available in China.

Cryopreserved Versus Non-Cryopreserved Peripheral Blood Haematopoietic Stem Cells for Autologous Stem Cell Transplantation in Multiple Myeloma: A Comparative Analysis from the Chronic Malignancies Working Party of EBMT and WBMT

Introduction: Globally, most transplant centres cryopreserve peripheral blood haematopoietic stem cells (PBSC) for use in a subsequent autologous haematopoietic cell transplant (AHCT), utilizing Dimethyl sulfoxide (DMSO) as a cryoprotectant. In contrast, non-vryopreserved PBSC are used in autologous transplants for multiple myeloma (MM) in some countries with more limited resources. We therefor compared standard MM AHCT outcomes between a large transplant centre in Algeria and EBMT registry data. Patients and Methods: This was a retrospective, international, multi-centre, matched-pair analysis between a tertiary transplant center in Algeria and EBMT-affiliated centres in 23 countries. A total of 437 consecutive adult patients undergoing a first MM AHCT in Oran, Algeria, between 2009 and 2020 using non-cryopreserved PBSC. All patients had given informed consent for approved research. PBSC mobilization was performed using G-CSF alone (10µg/kg) for 5 days. Stem cell collection was performed on either the Cobe Spectra or Optia using standard protocols. PBSCs were stored in a 4°C refrigerator immediatly post-collection. PBSC viability was calculated by standard Trypan Blue and flow cytometric techniques. The conditioning regimen was either Melphalan 140 mg/m 2 or 200 mg/m 2. PBSCs were infused 24 hours following Melphalan administration. Patients from Oran were matched to a maximum of 4 patients from an overall cohort of 64,030 patients from 420 EBMT-affiliated centres receiving cryopreserved stem cells over the same time-period. Pair matching was based on the following criteria: (1) patient gender (M,F), (2) MM sub-classification (IgG, IgA, light-chain only), (3) disease status at AHCT (CR, VGPR, PR, relapse/progression), (4) Melphalan conditioning dosage (140 or 200), (5) interval from diagnosis to AHCT, (6) date of AHCT, and (7) age at AHCT. Exact matching was used for the first four variables; propensity score matching was used for the remaining three. Primary endpoints were neutrophil and platelet engraftment as defined by standard EBMT criteria. Secondary endpoints included non-relapse mortality (NRM). The cumulative incidence of neutrophil and platelet engraftment was estimated using the crude cumulative incidence estimator with death was as competing event. The same method was used to estimate NRM as a competing event. Groups were compared using Gray's test. Results: In Oran, 437 MM patients were autografted between 2009 and 2020. Induction regimens (available in 436/437) were heterogeneous (VAD (11.2%), VD (13.3%), CTD (1.4%), VTD (43.1%), VRD (1.4%), VCD (28.0%), TD (0.5%), PAD (0.5%) or others (0.7%)) reflective of local practice. Most patients had one line of induction therapy (n=333 (76.4%); 98 patients (22.5%) had a second line of therapy prior to mobilization. The mean number of collection procedures was two (range (r), 1-3). The average PBSC viability was 95% (r, 93.8-98.5%). Complete matching variable data was available in 405 Oran patients (93%) and 19/405 (4.7%) could not be matched to EBMT patients. These were mostly younger patients (16/19&amp;lt;50 years at AHCT) who received low dose melphalan (17/19 received 140 mg/m 2 melphalan). Of the 386 patients, 357 patients had the required matches of 4 patients from the EBMT database and were used in this analysis. For the patients from Oran, the median dose of PBSCs collected was 3.2x10 6 CD34+ cells/kg (interquartile range (IQR, 2.4-4.5); for EBMT patients (available in 12%), it was 3.7x10 6CD34+ cells/kg (IQR, 2.8-4.9) (p=0.22). Regarding engraftment kinetics, the median times to neutrophil engraftment for the non-cryopreserved and EBMT cryopreserved cohorts were 12 (IQR, 11 to 14) days, and 12 (IQR, 11 to 13) days, respectively (p=0.11). Moreover, no significant difference was evident in the median time to platelet engraftment&amp;gt;20x10 9/L: non-cryopreserved 12 (r, 11 to 14) days and EBMT cryopreserved 12 (r, 11 to 14) (p=0.39) (Figure 1). Non-relapse mortality at day 100 (NRM) rate was 1%(0-2%) in Oran and 1% (1-1%) in EBMT (p=0.4). Conclusion: This large co-operative study between Oran and EBMT found that neutrophil and platelet engraftment rates were similar in the cryopreserved and non-cryopreserved matched cohorts. Moreover, there was no difference in NRM. The use of non-cryopreserved PBSC for MM AHCT in countries with limited resources is more straighforward and less costly.

Measurable Residual Disease Status By Clonotypic Mass Spectrometry with Easym Assay Predicts Outcomes Following Autologous Hematopoietic Cell Transplant in Multiple Myeloma

Bone marrow (BM)-based measurable residual disease (MRD) has been established as one of the most important dynamic prognostic markers in multiple myeloma (MM). However, the necessity of bone marrow biopsies limits the feasibility of frequent MRD monitoring. Consequently, there is an urgent unmet need for peripheral blood-based MRD testing for serial monitoring of disease response to allow tailored therapy for patients achieving deep remissions. Quantification of myeloma (M)-protein using mass spectrometry (MS) is a promising approach for peripheral blood-based MRD monitoring due to its exceptional analytical sensitivity. Prior studies have examined the use of MALDI-TOF-based methods, which relies on the mass distribution of intact immunoglobulins light chains and is approximately 1-log more sensitive than traditional testing. However, recent advances in MS technology have allowed determination and tracking of a “clonotypic” MS signature in the peripheral blood which is highly sensitive and patient-specific (Liyasova et al, CCR 2021). Prior reports have demonstrated the feasibility of this approach, but data supporting the association of blood-based clonotypic MS MRD with clinical outcomes is currently lacking. Consequently, we performed a large retrospective analysis of patients enrolled in our institutional MM tissue bank to determine the association of clinical outcomes with clonotypic MS-based MRD testing (EasyM, Rapid Novor, Kitchener, ON). We identified patients in our institutional tissue bank who met the following criteria: 1) diagnosis of MM, 2) underwent autologous hematopoietic cell transplant (AHCT), 3) M-protein ≥0.2 g/dL by serum protein electrophoresis (SPEP) or &amp;gt;20 mg/dL (light chain) at diagnosis, 4) had no detectable M-protein by SPEP at day +100 and 5) had adequate samples for analysis collected at day +100 after AHCT. Patients were included regardless of M-protein isotype. Baseline and follow up samples were analyzed by Rapid Novor without access to the clinical outcomes. Percent residual EasyM at day +100, in respect to baseline EasyM, was used as the independent variable to predict Progression-free survival (PFS). 95 patients were included in the analysis. Median age was 63, 88% were White and 61% were male. 64% were IgG, 20% IgA and 16% were with light chain (LC) MM. 26%, 62% and 12% were R-ISS stage I, II and III, respectively. High-risk cytogenetics were present in 32%. 97% had received proteasome inhibitors, 89% received immunodulatory agents and 13% anti-CD38 antibodies prior to AHCT. The median year of transplant was 2018 (range: 2008 - 2022). 93% patients received AHCT as part of frontline therapy. 66% were in CR or better following AHCT. 95% received maintenance after AHCT. 9 patients had non-quantifiable EasyM at follow up and were excluded from derivation of the MRD definition. Of the remaining 86, patients with IgA/LC and IgG disease had significant different percent residual EasyM following AHCT (median: 0.19% vs. 1.00%, p &amp;lt; 0.001). A cutoff of 1.036% residual EasyM was derived for IgG and 0.048% residual EasyM for IgA/LC patients was determined to fit the PFS data best, and based on these cutoffs, 41 patients (47%) were MRD negative by EasyM. The incidence of MRD negativity between IgG and IgA/LC was similar (55% vs. 32%). MRD positivity by EasyM was a strong predictor of PFS following AHCT (Figure 1) (HR: 2.249, p = 0.017). The median PFS in MRD positive patients was 3.4 years versus not reached in MRD negative patients (log rank: p = 0.014) (Figure 1). Our study is the first, to our knowledge, to demonstrate the clinical utility of peripheral blood-based clonotypic mass spectrometry to predict outcomes for patients with MM. Notably, our results suggest that different cutoffs should be employed for IgG and IgA/LC myeloma if drawn at day +100 after transplant. This is possibly due to the differing half-lives of these molecules. Significant additional questions remain, including the utility of ongoing monitoring at multiple time points and the optimal time post-AHCT to assess for MRD, especially in patients with IgG myeloma. Additionally, these findings require prospective validation in an independent cohort of patients to demonstrate wider applicability.

P-130 Retrospective assessment of outcomes with autologous bone marrow transplant in multiple myeloma - Real world data of 23 years

P-130 Retrospective assessment of outcomes with autologous bone marrow transplant in multiple myeloma - Real world data of 23 years

P-144 Busulfan plus melphalan versus high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma with high-risk features (KMM 2015)

P-144 Busulfan plus melphalan versus high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma with high-risk features (KMM 2015)