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Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m 2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: In autologous stem cell transplant (ASCT)-eligible myeloma patients, prolonged induction does not necessarily improve the depth of response., Method: We analyzed 1222 ASCT patients who were classified based on (a) the interval between induction and stem cell collection, (b) the type of induction regimen: BID (Bortezomib, IMiDs, and Dexamethasone), Bortezomib-based, or CTD (Cyclophosphamide, Thalidomide, and Dexamethasone), and (c) the time to best response (Early ie, best response within 4 or 5 months, depending on the regimen vs Late; Good ie, VGPR or better vs Poor)., Results: The length of induction treatment required to achieve a Good response did not affect PFS (P = .65) or OS (P = .61) post-ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months (P = .31), and median OS 81.7, 92.7, and 77.4 months, respectively (P = .83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, P-value = .02). However, achieving a Good response at induction was associated with a better response (≥VGPR) post-transplant., Conclusion: The kinetics of response did not affect outcomes., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n = 446), auto-auto (n = 105), or auto-allo (n = 72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45-58%) for single auto, 60% (95% CI, 49-72%) for auto-auto, and 67% (95% CI, 53-80%) for auto-allo (p = 0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12-22%), 33% (95% CI, 22-43%), and 34% (95% CI, 21-38%; p = 0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p = 0.007) and auto-allo (HR, 0.45; p = 0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p = 0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p = 0.097). No significant difference in OS was identified between the groups in patients with del(17p).

Objectives: The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma-reduced intensity conditioning (RIC), non-myeloablative (NMA), myeloablative conditioning (MAC) or Auto-AlloHCT-on outcomes in patients who had had a prior autologous transplant., Methods: A retrospective analysis of the EBMT database (1991-2012) was performed., Results: A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto-Allo transplants. At a median follow-up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%-47%), 45% (95% CI 32%-57%), 19% (95% CI 6%-32%) and 34% (95% CI 17%-51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276)., Conclusion: From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Plerixafor plus granulocyte-colony stimulating factor (G-CSF) enhances the mobilization of hematopoietic stem cells (HSCs) for collection and subsequent autologous hematopoietic stem cell transplantation (HSCT) in patients with multiple myeloma (MM). This international, multicenter, noninterventional registry study (NCT01362972), evaluated long-term outcomes for MM patients who received plerixafor versus other mobilization regimens. The comparisons were: G-CSF + plerixafor (G-CSF + P) versus G-CSF-; G-CSF + P versus G-CSF + chemotherapy (G-CSF + C); and G-CSF + P + C versus G-CSF + C. Propensity score matching was used to balance groups. Primary outcome measures were progression free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR) after transplantation. After propensity matching, 77 versus 41 patients in the G-CSF + P versus G-CSF cohorts, 129 versus 129 in the G-CSF + P versus G-CSF + C cohorts, and 117 versus 117 in the G-CSF + P + C versus G-CSF + C cohorts were matched, respectively. Propensity score matching resulted in a smaller sample size and imbalances were not completely overcome. For both PFS and OS, the upper limits of the hazard ratio 95% confidence intervals exceeded prespecified boundaries; noninferiority was not demonstrated. CIR rates were higher in the plerixafor cohorts. G-CSF + P remains an option for the mobilization of HSCs in poor mobilizers with MM with no substantial differences in PFS, OS, and CIR in comparison with other regimens.

To evaluate the outcomes of salvage third autologous stem cell transplantation (ASCT) in patients with relapsed multiple myeloma. We analyzed 570 patients who had undergone a third ASCT between 1997 and 2010 (European Society for Blood and Marrow Transplantation data), of whom 482 patients underwent tandem ASCT and a third ASCT at first relapse (AARA group) and 88 patients underwent an upfront ASCT with second and third transplantations after subsequent relapses (ARARA group). With a median follow-up after salvage third ASCT of 61 months in the AARA group and 48 months in the ARARA group, the day +100 nonrelapse mortality in the 2 groups was 4% and 7%, the incidence of second primary malignancy was 6% and 7%, the median progression-free survival was 13 and 8 months, and median overall survival (OS) was 33 and 15 months. In the AARA group, according to the relapse-free interval (RFI) from the second ASCT, the median OS after the third ASCT was 17 months if the RFI was <18 months, 37 months if the RFI was between 18 and 36 months, and 64 months if the RFI was ≥36 months (P < .001). In the ARARA group, the median OS after the third ASCT was 7 months if the RFI was <6 months, 13 months if the RFI was between 6 and 18 months, and 27 months if the RFI was ≥18 months (P < .001). In a multivariate analysis of the AARA group, the favorable prognostic factor was an RFI after second ASCT of ≥18 months. Progressive disease and a Karnofsky Performance Status score of <70 at third ASCT were unfavorable factors. A salvage third ASCT is of value for patients with relapsed myeloma, particularly for those with a long duration of response and chemosensitive disease at the time of transplantation., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first-line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received up-front single (n=3391) or tandem transplantation (n=353) between 2005 and 2014 with available data on extramedullary involvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n=682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%). More patients with extramedullary organ involvement had multiple involved sites (≥2; P <0.001). In a comparison of patients with single sites with patients without the disease, up-front transplantation resulted in at least similar 3-year progression-free survival (paraskeletal: P =0.86, and extramedullary organ: P =0.88). In single paraskeletal involvement, this translated less clearly into worse 3-year overall survival ( P =0.07) while single organ involvement was significantly worse ( P =0.001). Multiple organ sites were associated with worse outcome ( P <0.001 and P =0.01). First-line treatment with tandem compared with single transplantation resulted in similar survival in patients with extramedullary disease at diagnosis ( P =0.13 for both)., (Copyright © 2018 Ferrata Storti Foundation.)

The advent of novel agents for multiple myeloma (MM) is cause for a re-examination of the incidence of second primary malignancies (SPMs). We examined the SPM rate in MM patients who were enrolled in the prospective observational CALM (Collaboration to Collect Autologous Transplant outcome in Lymphoma and Myeloma) study. Between 2008 and 2012, 3204 patients with MM underwent a first autologous hematopoietic stem cell transplantation. Plerixafor was used as a mobilizing agent for patients with poor (or potentially poor) stem cell mobilization as defined by the respective centers. A total of 135 patients developed SPMs, with a cumulative incidence of 5.3% (95% confidence interval, 4.4 to 6.3) at 72 months. Ninety-four patients developed solid tumors, 30 developed hematologic malignancies, and 11 developed an SPM of an unknown type. The cumulative incidence of known hematologic and solid malignancies were 1.4% and 3.6%, respectively, at 72 months. In a univariate analysis, use of radiotherapy, type of induction regimen, hematopoietic stem cell dose, poor mobilizer status, plerixafor use, and sex did not influence the cumulative incidence of SPMs. Only age over 65 years was statistically associated with an increased incidence. Overall, the incidence of SPMs was comparable to earlier estimations of SPMs in MM., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Melphalan at a dose of 200 mg/m 2 is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140 mg/m 2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine whether melphalan 200 mg/m 2 and melphalan 140 mg/m 2 are equally effective and tolerable in clinically relevant patient subgroups we analyzed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, hematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 mg/m 2 (n=245) and melphalan 200 mg/m 2 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 mg/m 2 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 mg/m 2 versus melphalan 140 mg/m 2 : 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favored melphalan 140 mg/m 2 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 mg/m 2 and melphalan 140 mg/m 2 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favor the use of melphalan 200 mg/m 2 or melphalan 140 mg/m 2 for key transplant outcomes (NCT01362972)., (Copyright© 2018 Ferrata Storti Foundation.)

We have recently reported on the outcome of autologous transplantation in the rare myelomas (IgD, IgE, IgM, and nonsecretory [NS]) but there is no real information on the outcome of these conditions after allogeneic transplantation. We used the European Group for Blood and Marrow Transplantation myeloma database to compare the outcomes after allogeneic transplantation of 1354 common myelomas (IgG, IgA, and light chain myeloma) with the outcome in 26 IgD myelomas and 52 NS myelomas. There was little difference between common and the IgD and NS myeloma patients with respect to prognostic factors although the IgD group had a higher beta 2 microglobulin at diagnosis, shorter time to transplantation, and more T cell depletion. IgD and NS patients had a significantly greater achievement of complete remission at conditioning but this did not translate into equivalent progression-free survival and overall survival for the IgD patients although the NS outcome was very similar to that of common myeloma. The PFS and OS of IgD, common, and NS myelomas appear similar after allogeneic transplantation, despite a tendency for higher early relapse rate in IgD myeloma. Allogeneic transplantation may, therefore, be an option to investigate in prospective observational studies., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Long-term follow-up of prospective studies comparing allogeneic transplantation to autologous transplantation in multiple myeloma is few and controversial. This is an update at a median follow-up of 96 months of the European Group for Blood and Marrow Transplantation Non-Myeloablative Allogeneic stem cell transplantation in Multiple Myeloma (NMAM)2000 study that prospectively compares tandem autologous/reduced intensity conditioning allogeneic transplantation (auto/RICallo) to autologous transplantation alone (auto). There are 357 myeloma patients up to age 69 years enrolled. Patients with an HLA-identical sibling were allocated to auto/RICallo (n = 108) and those without to auto alone (n = 249). At 96 months progression-free survival (PFS) and overall survival (OS) were 22% and 49% vs 12% (P = .027) and 36% (P = .030) with auto/RICallo and auto respectively. The corresponding relapse/progression rate (RL) was 60% vs 82% (P = .0002). Non-relapse mortality at 36 months was 13% vs 3% (P = .0004). In patients with the del(13) abnormality corresponding PFS and OS were 21% and 47% vs 5% (P = .026), and 31% (P = .154). Long-term outcome in patients with multiple myeloma was better with auto/RICallo as compared with auto only and the auto/RICallo approach seemed to overcome the poor prognostic impact of del(13) observed after autologous transplantation. Follow up longer than 5 years is necessary for correct interpretation of the value of auto/RICallo in multiple myeloma.

Purpose: This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT)., Patients and Methods: Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m(2) intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months)., Results: Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P 0.001), and the median duration of response was longer (17.9 v 13.4 months; P.04) [corrected].The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia., Conclusion: VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.

Purpose: Results of allogeneic stem-cell transplantation (allo) in myeloma are controversial. In this trial autologous stem-cell transplantation (auto) followed by reduced-intensity conditioning matched sibling donor allo (auto-allo) was compared with auto only in previously untreated multiple myeloma., Patients and Methods: In all, 357 patients with myeloma up to age 69 years were enrolled from 2001 to 2005. Patients with an HLA-identical sibling donor were allocated to the auto-allo arm (n = 108) and patients without a matched sibling donor were allocated to the auto arm (n = 249). Single (n = 145) or tandem (n = 104) auto was optional. Conditioning for the auto arm was melphalan 200 mg/m(2); conditioning for the allo arm was total-body irradiation 2 Gy plus fludarabine 30 mg/m(2)/d for 3 days. Median follow-up time was 61 months. Primary end point was progression-free survival., Results: Progression-free survival at 60 months was significantly better with auto-allo than with auto [corrected] alone (35% v 18%; P = .001), as was the risk of death and of relapse in the long term (P = .047 and P = .003, respectively). Overall survival at 60 months was 65% versus 58%, and relapse incidence was 49% versus 78%. Complete remission rates were 51% and 41%, respectively (P = .020). Nonrelapse mortality at 24 months was 12% after auto-allo compared with 3% in the auto group (P < .001). The incidence of grade 2 to 4 acute graft-versus-host disease (GvHD) was 20%, and the incidence of limited and extensive chronic GvHD was 31% and 23%., Conclusion: In patients with previously untreated multiple myeloma, long-term outcome with respect to progression-free survival, overall survival, and relapse rate is superior after auto-allo compared with auto only. Nonrelapse mortality is at a reasonable level in both groups.

Background: As rare myelomas, i.e. the IgD, IgE, IgM and non-secretory forms, constitute only a small proportion of any study, relatively little is known about their prognosis in the era of peripheral stem cell transplantation., Design and Methods: We used the European Group for Blood and Marrow Transplantation Myeloma Database to compare the outcome following autologous transplantation of over 20,000 patients with common myelomas (IgG, IgA and light chain myeloma) with the outcome of patients with rare myelomas: 379 IgD, 13 IgE, 72 IgM and 976 non-secretory cases., Results: The study confirms the multiple adverse prognostic factors seen in IgD myeloma. Somewhat surprisingly, patients with IgD and non-secretory myeloma both had higher complete remission rates before and after transplantation than patients with common myelomas. However, while the overall survival of patients with non-secretory myeloma was similar to that of the patients with common myelomas, the survival of patients with IgD myeloma was significantly worse (although better than survival rates reported for non-transplanted patients); this was due to higher transplant-related mortality and relapse/progression rates. The post-transplantation survival of patients with IgE or IgM myeloma appears to be very poor., Conclusions: This study provides data on the biological features of rare myelomas. The overall survival of patients with IgD, IgE or IgM myeloma is poor following autologous transplantation but substantially better than that reported for patients who were not transplanted.

Objective: Stem cell transplantation has a place in the management of many patients with hematological disorders, but is no longer the final and definitive treatment for most of these individuals. The relapsing patient may be offered further therapy, and evaluating the contribution of the treatments available has become statistically challenging. This study was designed to evaluate further the benefit and timing of double autologous transplantation in the management of patients with myeloma., Materials and Methods: We investigated the potential benefit of a second autologous transplantation for myeloma before relapse or progression ("elective" transplantation) and the importance of the timing of the procedure using a multistate approach. We used data from 7452 patients with myeloma who received autologous transplantation and who were reported to the registry of the European Group for Blood and Marrow Transplantation., Results: With use of statistical and visual models, the multistate approach shows the benefit of being able to undergo a second transplantation within 12 months of the first transplantation., Conclusion: Our study focuses on the importance of appropriate statistical analysis and illustrates how use of the Cox model within a multistate framework may be applied to the assessment of the role of an intermediate event in the disease process. The study illustrates both mathematically and visually the improved survival resulting from undertaking an elective second transplantation in patients with myeloma as soon as medically prudent-usually within 3 to 6 months of the first transplantation.

Background and Objectives: Peripheral blood stem cells (PBSC) following reduced intensity conditioning (RIC) are being increasingly used for allogeneic transplantation in multiple myeloma. The purpose of this study was to compare outcome of patients transplanted with either PBSC or bone marrow (BM) following RIC or myeloablative conditioning (MAC)., Design and Methods: Data from 1,667 patients who had received an allogeneic identical sibling donor transplant for multiple myeloma from 1994 to 2003 were analyzed. Comparisons were made between results of PBSC and BM transplants after conditioning with RIC or MAC., Results: The engraftment rate was faster with PBSC than with BM (median: 14 and 18 days for neutrophils and 15 and 25 days for platelets respectively) irrespectively of whether RIC or MAC was used. The incidence of acute graft-versus-host disease (GVHD) did not differ significantly between the groups while chronic GVHD was more prevalent in PBSC recipients irrespectively of whether they had RIC or MAC. Non-relapse mortality did not differ between PBSC and BM recipients, but was significantly higher in those treated with MAC than in those given RIC irrespectively of the cell source. The relapse/progression rate did not differ between PBSC and BM recipients, but was significantly higher in those given RIC, irrespectively of the cell source. There was no significant difference in overall or progression-free survival between patients given PBSC or BM transplants., Interpretation and Conclusions: Although transplantation of PBSC is associated with faster engraftment and more frequent chronic GVHD, overall survival, non-relapse mortality, relapse/progression and progression-free survival are similar to those following BM transplants. However both PBSC and BM transplants are associated with lower non-relapse mortality, lower response rate and higher relapse/progression if RIC is used instead of MAC.

Despite the widespread adoption of reduced-intensity conditioning (RIC) for myeloma, there are few data comparing outcomes with RIC with myeloablative conditioning (MAC). We report the outcomes of patients undergoing allogeneic transplantations for myeloma and reported to the EBMT. A minimum data set was available on 320 RIC and 196 MAC allografts performed between 1998 and 2002. The RIC patients were older (51 vs 45 years) with more progressive disease (28% vs 21%) and more had received a prior transplant (76% vs 11%). In addition, there was a longer time to transplantation and an increased use of peripheral blood and T-cell depletion. For RIC and MAC, respectively, the nonrelapse mortality (NRM) at 2 years was 24% and 37% (P = .002); overall survival, 38.1% and 50.8% (not significant [ns]); and progression-free survival (PFS), 18.9% and 34.5% (P = .001). On multivariate analysis, RIC was associated with a reduction in NRM (HR, 0.5), but this was offset by an increase in relapse risk (HR, 2.0), and the conditioning intensity did not impact on overall survival or retain significance for PFS. These data suggest that there is a continuing need to investigate dose intensity in the conditioning for myeloma allografts.

We compared antithymocyte globulin (ATG) with alemtuzumab in 73 patients with multiple myeloma, who underwent reduced conditioning with melphalan/fludarabine, followed by allogeneic stem cell transplantation from human leucocyte antigen-matched or -mismatched unrelated donors. The ATG group had more prior high-dose chemotherapies (P < 0.001), while bone marrow was used more as the stem cell source in the alemtuzumab group (P < 0.001). Alemtuzumab resulted in faster engraftment of leucocytes (P = 0.03) and platelets (P = 0.02) and in a lower incidence of acute graft versus host disease (GvHD) grades II-IV (24% vs. 47%, P = 0.06). More cytomegalovirus (CMV) seropositive patients in the alemtuzumab group experienced CMV reactivation (100% vs. 47%, P = 0.001). The cumulative incidence of treatment-related mortality at 2 years was 26% [95% confidence interval (CI) = 12-37%] for ATG vs. 28% (95% CI = 15-55%) for alemtuzumab, P = 0.7. There was no significant difference in the estimated 2-year overall and progression-free survival between ATG and alemtuzumab: 54% (95% CI: 39-75%) vs. 45% (95% CI: 28-73%) and 30% (95% CI: 16-55%) vs. 36% (95% CI: 20-62%) respectively. In multivariate analysis, treatment with alemtuzumab had a higher risk for relapse (hazard ratio: 2.37; P = 0.05) while killer immunoglobulin-like receptor (KIR)-ligand mismatch was protective for relapse (P < 0.0001). We conclude that alemtuzumab produced less acute GvHD, but higher probability of relapse. The data implicated a major role of KIR-ligand mismatched transplantation in multiple myeloma.

Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0–100 days, 101 days–1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4–108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and <2.31 cases per 100 patient-years from the 101st day. At 100 days after ASC T, 45.7% of patients had complications, with infectious events being twice as frequent as non-infectious complications. Bacterial infections (6.5 cases per 100 patient-years, 95% CI: 6.1–7.0) and gastrointestinal complications (4.7 cases per 100 patient-years, 95% CI: 4.3–5.1) were the most common early events. The pattern of complications changed with time from ASCT. The presence of complications after ASCT was not associated with overall survival. Conclusions: Our data provide a solid basis for comparing ASCT-related complications to those caused by emerging treatments in multiple myeloma, such as CAR T-cell therapy and other immunotherapies. [ABSTRACT FROM AUTHOR]

Novel drugs have improved survival for patients with multiple myeloma in recent years. However, the disease is still fatal. Allogeneic stem cell transplantation (Allo) has proven to cure some patients with the disease, but its role is controversial due to relatively high transplant-related toxicity and mortality (nonrelapse mortality, NRM). Using nonmyeloablative reduced-intensity conditioning (RIC), both toxicity and NRM can be reduced, and RICAllo is, therefore, an option for subgroups of patients. Upfront tandem autologous/RICAllo (Auto/RICAllo) was shown to be superior to single Auto or tandem Auto/Auto in both progression-free (PFS) and overall survival (OS) in two prospective studies with long-term follow-up, while three similarly designed studies did not detect a difference. A recent update of pooled patient data from four of these studies showed significantly superior PFS and OS with Auto/RICAllo. Importantly, none of these studies showed inferior results with Auto/RICAllo in patients less than 70 years of age. Auto/RICAllo appears to overcome some poor risk cytogenetic markers. Encouraging results have also been seen in treatment of relapsed patients. Combining Allo with new proteasome inhibitors and immunomodulatory drugs may further improve results. Other encouraging new cell therapies such as with CAR T-cells, NK- and CAR NK-cells may well have a place in combination with RICAllo. Such studies are warranted. [ABSTRACT FROM AUTHOR]