Transplantation For Multiple Myeloma Research Articles

Historical Perspective of High-Dose Therapy Followed by Autologous Stem Cell Transplantation in Multiple Myeloma.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) has become part of standard of care (SOC) in newly diagnosed multiple myeloma (MM). In this review we provide a historical perspective on ASCT since its introduction in the 1990s. Overall Survival (OS) benefit for HDT followed by ASCT was demonstrated in studies comparing HDT with ASCT to standard-dose therapy (SDT) before the era of novel agents. Conditioning is done with melphalan 200 mg/m2 (MEL200). Lower doses (MEL140, MEL150) for older patients with comorbidities are safe and have comparable results. The addition of busulfan to melphalan improves progression survival (PFS) but not OS. HDT with ASCT after induction with novel agents prolongs PFS but not OS compared to SDT alone. The benefit is more evident in patients with high-risk cytogenetics. Mobilization can be achieved with Granulocyte-Colony Stimulating Factor (GCSF) alone, but is improved with the addition of chemotherapy. Plerixafor reduces mobilization failure and enables sufficient stem-cell collection after induction with novel agents. ASCT is safe with a low rate of mortality (1%), and selected patients can be managed as outpatients. HDT followed by ASCT remains part of SOC due to its PFS benefit and relatively low 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)

The Effects of Premedication with Desipramine on Bone Marrow Mobilization for Autologous Bone Marrow Transplantation in Multiple Myeloma

Background: Multiple myeloma (MM) management includes primary chemotherapy, followed by autologous bone marrow transplantation (ABMT) if the bone marrow gets cleared of cancerous cells. In some cases disease relapse may occur disease relapse may occur if complete clearance is not achieved. Transplantation was primarily performed through the bone marrow; however, peripheral blood has become more favored due to its safety and convenient collection in case of appropriate bone marrow mobilization which is a challenging issue. Objectives: The current study was aimed to investigate the effectiveness of desipramine application for bone marrow mobilization in multiple myeloma (MM) who were candidate for autologous bone marrow transplantation (ABMT). Methods: The current randomized clinical trial involved 122 MM patients who were candidate for ABMT. The participants were divided into two intervention groups: the first group (n = 63) received G-CSF only treatment, while the second group (n = 59) received a similar G-CSF treatment plus desipramine. The first group received 30 microgram intravenous G-CSF for five days and the second one was treated with G-CSF with similar pattern in combination with daily 100 mg desipramine initiated within three days before G-CSF treatment and continued until the last dose of G-CSF. CD34+ cells and complete blood cells and differentiation were assessed by the end of the interventions. Results: The findings of the study show that the number of CD34+ cells, white blood cells (WBC) and platelet (PLT) count were remarkably higher among the patients receiving the combination therapy compared to the G-CSF only treated group (P-value &lt; 0.001) within 5 days after the interventions; however, no significant differences were observed between the two groups when considering the stage of the disease and the frequency of chemotherapy sessions (P-value &gt; 0.05). Conclusions: Desipramine application led to significantly increased levels of CD34+ cells as the representatives of bone marrow mobilization. Besides, the patients treated with this regimen had higher serum levels of WBC and PLT; however, the disease stage and the number of chemotherapy sessions did not affect the response to the treatment.

Long-term outcomes of allogeneic stem cell transplant in multiple myeloma

Allogeneic stem cell transplant (allo SCT) for multiple myeloma (MM) is potentially curative in some, while toxic in many others. We retrospectively analyzed 85 patients diagnosed with MM who underwent allo SCT as frontline or salvage therapy between 2000 and 2022 at Mayo Clinic Rochester and examined patient outcomes and prognostic markers. Overall survival (OS), progression free survival (PFS), treatment related mortality (TRM), and relapse rates (RR) were estimated using the Kaplan Meier method and competing risk models. Median follow-up was 11.5 years. Median OS and PFS were 1.7 and 0.71 years, respectively. Five-year OS and PFS were 22.2% and 15.1%, respectively. One-year TRM was 23.5%. Twelve patients demonstrated durable overall survival, living 10+ years beyond their allo SCT. This subgroup was more likely to have no or one prior auto SCT (p = 0.03) and to have been transplanted between 2000 and 2010 (p = 0.03). Outcomes were poor in this cohort with long follow-up, with few patients surviving 5 years or more, and most relapsing or dying within 2 years. We would expect better outcomes and tolerability with an expanded array of novel therapeutics and would prefer them to allo SCT.

Characteristics and outcome of infectious complications after autologous hematopoietic cell transplantation in multiple myeloma patients.

Infections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post-AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries. We performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient-specific, disease-specific, and transplant-specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen-related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100. Ninety-five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33-68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4-144). Eighty-nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile-associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9-14) and 12 days (range 9-23), respectively. The median duration of hospital stay was 16 days (range 9-29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant-related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10vs. day +11) and platelet engraftment (day +11vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression-free survival of the study population at 5 years were 72.7% and 64.8%, respectively. This study shows that the incidence of infections and TRM are higher in MM patients from lower-middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis.

Efficacy and safety of tandem autologous stem cell transplantation in multiple myeloma: a retrospective single-center analysis.

Efficacy and safety of tandem autologous stem cell transplantation in multiple myeloma: a retrospective single-center analysis.

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).

Despite the development of effective agents for multiple myeloma (MM), the management of patients with high-risk MM (HRMM) is challenging. High-dose treatment followed by autologous stem cell transplantation (ASCT) is regarded as upfront treatment for transplant-eligible patients with HRMM. In the present study, we retrospectively investigated the efficacies of two conditioning regimens for upfront ASCT in newly diagnosed patients with MM and high-risk features: high-dose melphalan (HDMEL; 200 mg/m2) and busulfan plus melphalan (BUMEL). In total, 221 patients underwent ASCT between May 2005 and June 2021; among these 221 patients, 79 had high-risk cytogenetic abnormalities. In patients with high-risk cytogenetics, BUMEL showed a tendency toward longer overall survival (OS) and progression-free survival (PFS) compared to HDMEL (median OS; not reached vs. 53.2 months; P = 0.091, median PFS; not reached vs. 31.7 months; P = 0.062). Additionally, multivariate analysis revealed that BUMEL was significantly associated with PFS (hazard ratio = 0.37, 95% confidence interval = 0.15-0.89, P = 0.026). We compared BUMEL with HDMEL in patients with other high-risk features, such as high lactate dehydrogenase level, extramedullary disease, and poor response to frontline therapy. Notably, among patients with less than very good partial response (VGPR) to frontline therapy, median PFS was significantly longer in the BUMEL group than in the HDMEL group (55.1 vs. 17.3 months, respectively; P = 0.011). These findings indicate that BUMEL may be an effective conditioning regimen for upfront ASCT in MM patients with high-risk cytogenetics; BUMEL may be more appropriate than HDMEL for patients with less than VGPR to frontline therapy.

Experience of a stem cell transplant in multiple myeloma: The patient and care partner perspective.

e18790 Background: Understanding patient experiences of their multiple myeloma (MM) disease journey, particularly related to the burden of autologous stem cell transplant (ASCT) and treatment recovery process, helps characterize unmet needs and quality of life of patients and their caregivers. A qualitative study of the experience of patients with MM who received ASCT and perspectives of caregivers was conducted. Methods: Recruited participants with MM were ≥18 years of age and received ASCT within the past 5 years or caregivers of patients who met these criteria. Two virtual focus group interviews were conducted, in which patients and caregivers were asked separately to narrate their disease journey starting with first symptoms and diagnosis, then focusing on the ASCT and recovery period. Results: A total of 16 participants, including 12 MM patients and 4 caregivers, were included. Nine participants (56.25%) were less than 60 years old, and eleven (68.75%) participants were female. Study participants were diverse in race/ethnicity; one-third of participants were Black and one-third comprised other minorities (Hispanic, Native Hawaiian, Asian, and Multiracial). Pain, weakness, and fractured bones (femur, hip, or spinal fractures) were common first symptoms. Other common patient-reported symptoms included high blood pressure, blurred vision, more frequent illnesses, unsteady gait, and anemia. The patients in the study were first diagnosed with MM in a variety of ways, mostly by a primary care physician and some in urgent care settings. The diagnosis process could take up to six months for some patients and commonly a community oncologist referred patients to a bone marrow transplant specialist, who was the primary driver in making ASCT decisions. Eight patients received their ASCT in an inpatient setting and four patients in an outpatient setting, with three eventually being hospitalized due to complications. Only one patient stayed in an outpatient setting the entire time. Initial recovery time after ASCT ranged from 2 weeks to 4 months; complete recovery took from 30 days to “never.” The most patient-reported difficulties during recovery time included nausea, loss of appetite, weakness, fatigue, and pain. Caregivers played an important role in the recovery process and often with negative financial impact related to missing work and travel expenses. Conclusions: Patients with MM who received ASCT and their caregivers perceived various unmet needs throughout their transplant journey. Post–stem cell transplant symptoms had a substantial impact on patients’ quality of life, especially with lengthy and challenging recovery. Innovative therapies are needed for newly diagnosed MM to reduce the burden of disease and enhance the quality of life for both patients and their caregivers.

Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial

Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34+ hematopoietic stem and progenitor cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 106 CD34+ cells kg–1 within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12–201.33, P < 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36–549.35, P < 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34+ HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov, NCT03246529