The impact of daratumumab pretreatment on multiple myeloma patients undergoing autologous transplantation.

The anti-CD38 antibody daratumumab (Dara) has been reported to improve the prognosis of multiple myeloma (MM) patients, but its use before autologous stem cell transplantation (ASCT) remains controversial. To clarify the prognostic impact of Dara before ASCT on MM, we performed a retrospective observational analysis. We analyzed 2626 patients who underwent ASCT between 2017 and 2020. In the comparison between patients not administered Dara (Dara- group) and those administered Dara (Dara+ group), the 1-year progression-free survival (PFS) rates were 87.4% and 77.3% and the 1-year overall survival (OS) rates were 96.7% and 90.0%, respectively. In multivariate analysis, age <65 years (p = 0.015), low international staging system (ISS) stage (p < 0.001), absence of unfavorable cytogenic abnormalities (p < 0.001), no Dara use before ASCT (p = 0.037), and good treatment response before ASCT (p < 0.001) were independently associated with superior PFS. In matched pair analysis, the PFS/OS of the Dara- group were also significantly superior. For MM patients who achieved complete or very good partial response (CR/VGPR) by Dara addition before ASCT, both PFS and OS significantly improved. However, in patients who did not achieve CR/VGPR before ASCT, the PFS/OS of the Dara+ group were significantly inferior to those of the Dara- group.

The lymphocyte/monocyte ratio predicts the efficacy of isatuximab plus pomalidomide in multiple myeloma patients.

BACKGROUND: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab. OBJECTIVE: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment. METHODS: We retrospectively analyzed the cases of 134 relapsed/refractory MM patients in the Kansai Myeloma Forum database who had received only a first isatuximab treatment. RESULTS: Among the 134 patients, an isatuximab, pomalidomide and dexamethasone (Isa-PD) regimen, isatuximab, carfilzomib and dexamethasone (Isa-KD) regimen and isatuximab and/or dexamethasone (Isa-D) regimen were used in 112, 15 and 7 patients, respectively. The median age at treatment, number of prior treatment regimens, and progression-free survival (PFS) were 71, 6, and 6.54 months, respectively. Multivariate analysis showed that the PFS under the Isa-PD regimen was longer in patients with higher lymphocyte/monocyte ratio (LMR ≥ 4), fewer prior treatment regimens (< 6), and no use of prior daratumumab treatment. The OS under the Isa-PD regimen was longer in patients with higher white blood cell counts (WBC counts ≥ 3000/µL) and higher LMR. The PFS under the Isa-D regimen was longer in patients with fewer prior treatment regimens in univariate analysis, but no parameters were correlated with PFS/OS under the Isa-KD regimen. CONCLUSION: We found that the patients with higher LMR (≥ 4) could obtain longer PFS and OS under the Isa-PD regimen. Other cohort studies of isatuximab treatment might be necessary to substantiate our results.

The impact of renal function on initial therapy in transplant-ineligible multiple myeloma patients.

The prognosis for multiple myeloma (MM) patients has improved with the advent of new drugs, but the prognosis with renal impairment (RI) is poor. The choice of treatment in such cases is critical, but there are no set criteria. We examined the impact of RI on initial therapy in transplant-ineligible MM patients. We selected symptomatic MM patients who met the following criteria: age ≥ 65 years, fit, and ineligible for transplantation from the database. We analyzed the impact of age, treatment, International Staging System (ISS) stage, karyotype abnormalities, performance status, and estimated glomerular filtration rate (GFR < 50 or ≥ 50 ml/min/1.73m2) on overall survival (OS). We also analyzed the OS by eGFR for each treatment. We selected 349 symptomatic MM patients. The regimens used were lenalidomide, bortezomib and dexamethasone (RVd), daratumumab, bortezomib, melphalan, and prednisolone (D-VMP), daratumumab, lenalidomide and dexamethasone (D-Rd) and daratumumab, bortezomib, and dexamethasone (D-Vd) in 184, 41, 74 and 50 patients, respectively. The median age was 74 years old; ISS stage was I/II/III in 85/112/131 patients; and 161 patients showed eGFR < 50. The OS was shorter with ISS stage III (p = 0.029) and eGFR < 50 (p < 0.001) by multivariate analysis. The OS under the RVd/D-Rd regimens were significantly shorter for patients with eGFR < 50, but OS under the D-VMP/D-Vd regimens were not significantly different between patients with eGFR < 50 and eGFR ≥ 50. The OS of the transplant-ineligible MM patients with higher ISS stage and RI was poor. Initial treatment with a D-VMP/D-Vd regimen might be less affected by RI.

Pretreatment blast-to-lymphocyte ratio as a prognostic marker for CD19/CD3-bispecific T cell-engaging antibodies (blinatumomab) treatment against relapsed or refractory B-precursor acute lymphoblastic leukemia.

Blinatumomab is an immunotherapy drug approved for the treatment of acute lymphoblastic leukemia. Since not all patients respond to blinatumomab, markers are needed to predict the efficacy of blinatumomab in individual patients. We hypothesized that the pre-treatment blast-to-lymphocyte ratio would predict blinatumomab efficacy. To examine this possibility, we conducted a post hoc analysis using data from the TOWER Clinical Trials (NCT02013167). Multivariate analysis showed that, along with the treatment groups, each of the following was independently correlated with superior progression-free survival: salvage-treatment phase, allogeneic stem cell transplantation, and pre-treatment ratio of bone marrow blasts-to-peripheral blood lymphocytes < 25.

Adverse impact of delay of platelet recovery after autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma and multiple myeloma.

BACKGROUND AIMS: The prognostic impact of platelet recovery after autologous hematopoietic cell transplantation (AHCT) on clinical outcomes remains to be elucidated. We aimed to clarify the impact of platelet recovery on clinical outcomes, risk factors of delayed platelet recovery and the necessary dose of CD34+ cells for prompt platelet recovery in each patient. METHODS: Using a nationwide Japanese registry database, we retrospectively analyzed clinical outcomes of 5222 patients with aggressive non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). RESULTS: At a landmark of 28 days after AHCT, a delay of platelet recovery was observed in 1102 patients (21.1%). Prompt platelet recovery was significantly associated with superior overall survival (hazard ratio [HR] 0.32, P < 0.001), progression-free survival (HR 0.48, P < 0.001) and decreased risks of disease progression (HR 0.66, P < 0.001) and non-relapse/non-progression mortality (HR 0.19, P < 0.001). The adverse impacts of a delay of platelet recovery seemed to be more apparent in NHL. In addition to the dose of CD34+ cells/kg, disease status, performance status and the hematopoietic cell transplant-specific comorbidity index in both diseases were associated with platelet recovery. We then stratified the patients into three risk groups according to these factors. For the purpose of achieving 70% platelet recovery by 28 days in NHL, the low-, intermediate- and high-risk groups needed more than 2.0, 3.0 and 4.0 × 106 CD34+ cells/kg, respectively. In MM, the low-risk group needed approximately 1.5 × 106 CD34+ cells/kg, whereas the intermediate- and high-risk groups required 2.0 and 2.5 × 106 CD34+ cells/kg to achieve about 80% platelet recovery by 28 days. CONCLUSIONS: A delay of platelet recovery after AHCT was associated with inferior survival outcomes.

Tandem autologous stem cell transplantation in elderly patients with myeloma: A multicenter retrospective analysis.

Tandem autologous stem cell transplantation (ASCT) has been reconsidered for high-risk patients with myeloma, and the eligibility criteria for up-front ASCT have been updated to include more elderly patients. This study aimed to evaluate the efficacy and tolerability of tandem ASCT in elderly patients with myeloma compared to tandem ASCT in young patients and single ASCT in elderly patients. A retrospective study using the Transplant Registry Unified Management Program database of the Japanese Society for Transplantation and Cellular Therapy, which included 64 elderly and 613 young patients who received tandem ASCT, and 891 elderly patients who received single ASCT, was conducted. The median overall survival (OS) over 38.5 months in the elderly and young patients who received tandem ASCT, and elderly patients who received single ASCT was 78.9, 92.5, and 77.1 months, respectively; no significant difference in the median OS was observed. The cumulative incidence of transplantation-related mortality was similar in the elderly and young patients receiving tandem ASCT. High-risk cytogenetic abnormality was not identified as a poor prognostic factor for OS in elderly patients who received tandem ASCT but in those who received single ASCT. Thus, tandem ASCT was effective and tolerable in elderly patients with myeloma.

Allogeneic stem cell transplantation for children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia in the tyrosine kinase inhibitor era.

The analysis of 165 children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia showed disease status at hematopoietic stem cell transplantation was a strong prognostic factor and clearly separated the patient outcomes.

Prognostic impact of complex karyotype on post-transplant outcomes of myelofibrosis.

Chromosomal abnormalities in the role of prognostic factor for transplant patients with myelofibrosis (MF) are not fully investigated. Regarding complex karyotype (CK), we retrospectively analyzed 241 patients with primary and secondary MF who received a first allogeneic hematopoietic cell transplantation (HCT). Based on an unfavorable karyotype in the Dynamic International Prognostic Scoring System, we compared the outcomes in 3 groups: favorable karyotype, unfavorable karyotype including CK (unfavorable-CK(+)), and unfavorable karyotype not including CK (unfavorable-CK(-)). Overall survival was significantly shorter in the unfavorable-CK(+) group (hazard ratio (HR) 2.49, 95% CI: 1.46-4.24, P < 0.001), whereas there was no difference between the unfavorable-CK(-) group and the favorable group (HR 0.57, 95% CI: 0.20-1.59, P = 0.28). In addition, a significantly higher proportion of patients in the unfavorable-CK(+) group did not achieve complete remission after HCT (P = 0.007). The cumulative incidence of disease progression was significantly higher in the unfavorable-CK(+) group (HR 2.5, 95% CI 1.6-3.92, P < 0.001), whereas that in the unfavorable-CK(-) group was comparable to that in the favorable group (HR 0.49, 95% CI 0.12-1.94, P = 0.31). Further investigations will be needed to clarify the impact of CK on transplant outcomes in MF.

The new generation tyrosine kinase inhibitor improves the survival of chronic myeloid leukemia patients after allogeneic stem cell transplantation.

The introduction of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) treatment has dramatically improved the prognosis of CML patients and reduced the number of patients receiving allogeneic stem cell transplantation (allo-SCT). However, the impact of the newest-generation TKIs on the overall survival (OS) after allo-SCT has not been well described. To investigate the beneficial effects of TKIs on the prognosis after allo-SCT, we conducted a retrospective observational study using the Transplant Registry Unified Management Program database in Japan. We analyzed 1188 patients (male/female: 738/450; median age: 44 years; range: 16-75) who underwent their first allo-SCT between January 2001 and December 2018. We divided the patients into two groups according to the TKI treatment used before allo-SCT: group 1 was treated with the first generation TKI imatinib; group 2 was treated with the second generation TKIs nilotinib, dasatinib, or bosutinib and/or the third generation TKI ponatinib. We compared the post allo-SCT OS between the two groups. The 3-year OS rates (95%CI) of groups 1 and 2 were 59.3% (54.8%-63.5%) and 65.8% (61.6%-69.6%), respectively (p = 0.017). Multivariate analysis confirmed that group 2 had superior OS after allo-SCT compared to group 1 (p = 0.002). Other factors associated with superior prognosis were age ≤65, performance status (PS) 0/1, a 6/6 HLA-matched donor and chronic-phase (CP) disease status at allo-SCT. A subgroup analysis showed poor prognoses for patients who could not obtain a molecular response before allo-SCT and patients with positive T315I mutation in the BCR/ABL gene. In group 2, early allo-SCT was correlated with superior OS in patients with a blast-crisis disease status at allo-SCT (p = 0.001). The cumulative incidence of non-relapse mortality rate significantly decreased in group 2 (p = 0.0005). The post allo-SCT OS was improved both by pre- and post-management of allo-SCT and by the introduction of newer TKIs.

Improved survival of multiple myeloma patients treated with autologous transplantation in the modern era of new medicine.

New drugs for multiple myeloma (MM) have dramatically improved patients' overall survival (OS). Autologous stem cell transplantation (ASCT) remains the mainstay for transplant-eligible MM patients. To investigate whether the post-ASCT prognosis of MM patients has been improved by new drugs, we undertook a retrospective observational analysis using the Transplant Registry Unified Management Program database in Japan. We analyzed 7323 patients (4135 men and 3188 women; median age, 59 years; range 16-77 years) who underwent upfront ASCT between January 2007 and December 2018. We categorized them by when they underwent ASCT according to the drugs' introduction in Japan: group 1 (2007-2010), group 2 (2011-2016), and group 3 (2017-2018). We compared the groups' post-ASCT OS. The 2-year OS rates (95% confidence interval [CI]) of groups 1, 2, and 3 were 85.8% (84.1%-87.4%), 89.1% (88.0%-90.1%), and 92.3% (90.0%-94.2%) (P < .0001) and the 5-year OS (95% CI) rates were 64.9% (62.4%-67.3%), 71.6% (69.7%-73.3%), and not applicable, respectively (P < .0001). A multivariate analysis showed that the post-ASCT OS was superior with these factors: age less than 65 years, performance status 0/1, low International Staging System (ISS) stage, receiving SCT for 180 days or less post-diagnosis, better treatment response pre-ASCT, later year of ASCT, and receiving SCT twice. A subgroup analysis showed poor prognoses for the patients with unfavorable karyotype and poor treatment response post-ASCT. The post-ASCT OS has thus improved over time (group 1 < 2 < 3) with the introduction of new drugs for MM. As the prognosis of high-risk-karyotype patients with ISS stage III remains poor, their treatment requires improvement.

Outcomes of ixazomib/lenalidomide/dexamethasone for multiple myeloma: A multicenter retrospective analysis.

OBJECTIVES: This study aimed to investigate real-world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM). METHODS: We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database. RESULT: At the start of IRd, the median age was 72 years, 66.7% of patients had IgG type, and the median number of prior therapies was 4, comprising bortezomib (85.4%) and lenalidomide (89.3%)-based regimens. Disease progression and adverse events accounted for treatment discontinuation in 46 and 32 patients, respectively. The median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 11.9 months. Sensitivity to bortezomib did not affect the PFS, whereas lenalidomide-refractory patients had significantly lower PFS than lenalidomide-sensitive patients, who were comparable to TOURMALINE-MM1 study. The patients with IgG type had significantly better PFS and OS than those with non-IgG type. CONCLUSION: This study presents the largest real-world data of patients treated with IRd in Asia. However, in real clinical practice, the patient background is different from the TOURMALINE-MM1 study, and IRd showed poor efficacy, especially in the non-IgG type and lenalidomide-refractory patients with RRMM.

Graft-Versus-Host Disease Amelioration by Human Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Is Associated with Peripheral Preservation of Naive T Cell Populations.

A substantial proportion of patients with acute graft-versus-host disease (aGVHD) respond to cell therapy with culture-expanded human bone marrow mesenchymal stromal/stem cells (BM-MSCs). However, the mechanisms by which these cells can ameliorate aGVHD-associated complications remain to be clarified. We show here that BM-MSC-derived extracellular vesicles (EVs) recapitulated the therapeutic effects of BM-MSCs against aGVHD. Systemic infusion of human BM-MSC-derived EVs prolonged the survival of mice with aGVHD and reduced the pathologic damage in multiple GVHD-targeted organs. In EV-treated GVHD mice, CD4+ and CD8+ T cells were suppressed. Importantly, the ratio of CD62L-CD44+ to CD62L + CD44- T cells was decreased, suggesting that BM-MSC-derived EVs suppressed the functional differentiation of T cells from a naive to an effector phenotype. BM-MSC-derived EVs also preserved CD4 + CD25 + Foxp3+ regulatory T cell populations. In a culture of CD3/CD28-stimulated human peripheral blood mononuclear cells with BM-MSC-derived EVs, CD3+ T cell activation was suppressed. However, these cells were not suppressed in cultures with EVs derived from normal human dermal fibroblasts (NHDFs). NHDF-derived EVs did not ameliorate the clinical or pathological characteristics of aGVHD in mice, suggesting an immunoregulatory function unique to BM-MSC-derived EVs. Microarray analysis of microRNAs in BM-MSC-derived EVs versus NHDF-derived EVs showed upregulation of miR-125a-3p and downregulation of cell proliferative processes, as identified by Gene Ontology enrichment analysis. Collectively, our findings provide the first evidence that amelioration of aGVHD by therapeutic infusion of BM-MSC-derived EVs is associated with the preservation of circulating naive T cells, possibly due to the unique microRNA profiles of BM-MSC-derived EVs. Stem Cells 2018;36:434-445.

[Successful Treatment with Pomalidomide, Bortezomib, and Dexamethasone in a Patient with Frail Refractory and Relapsed Multiple Myeloma with Extramedullary Disease].

An 85-year-old female was diagnosed with multiple myeloma(MM)(IgG-l)with t(4 ;14)(p16;q32)in 200X. She received bortezomib with dexamethasone(Vd)therapy and lenalidomide with dexamethasone(Ld)therapy, and she subsequently maintained a very good partial response(VGPR). On day 731, she experienced relapse and was treated with 2 courses of elotuzumab with Ld therapy. However, on day 794, she experienced relapse with plasmacytoma, and was treated with 2 courses of pomalidomide and low-dose dexamethasone(Pd), 2 courses of cyclophosphamide with Pd(PCd), and bortezomib with Pd(PVd)therapies. After 3 courses of PVd therapy, she achieved PR. She has continued to receive 11 courses of PVd therapy and has not suffered any adverse events(BGrade 3). These findings suggest that PVd therapy is a relatively safe and highly efficacious treatment for frail patients with relapsed and refractory MM who have previously received both lenalidomide and bortezomib. Further studies are needed to establish treatment efficacy and safety in frail patients with relapsed and refractory MM with extramedullary disease.

Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation.

Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.

[Suppression of tumor antigen-specific T cell immune responses by regulatory T cells].

CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells(Tregs)play important roles in maintaining self-tolerance in vivo by suppressing self antigen- reactive T cells. In the tumor microenvironment, tumor cells produce several chemokines and attract Tregs, resulting in suppression of tumor antigen-specific cytotoxic CD8⁺ T cell activation. Controlling the suppressive function of Tregs to recover anti-tumor immune responses in the tumor microenvironment is critical to improve the efficiency of cancer immunotherapy. Many immune-checkpoint blockade reagents, including antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA- 4), programmed cell death (PD)-1, and PD-L1, have been tested in the clinic and elicit clinical responses in several types of cancers. Importantly, clinical responses in melanoma patients treated with an anti-CTLA-4 antibody were associated with a reduced number of Tregs in the tumor microenvironment. Therefore, in addition to activating or expanding antigen-specific cytotoxic T cells, modulating the number and/or function of Tregs in the tumor microenvironment is the next important challenge in the field of cancer immunotherapy.

Updated comparable efficacy of cord blood transplantation for chronic myelomonocytic leukaemia: a nationwide study.

Chronic myelomonocytic leukaemia (CMML) is a haematological malignancy with a poor prognosis. Allogeneic haematopoietic stem cell transplantation remains the only curative approach. Without human leucocyte antigen-matched related sibling donors, the optimal alternative donor has yet to be established. Although unrelated bone marrow transplantation (UBMT) has been extensively studied, cord blood transplantation (CBT) for CMML remains largely unexplored. This nationwide retrospective study compared the outcomes of UBMT and single-unit umbilical CBT in patients with CMML. This study included 118 patients who underwent their first allo-HSCT during 2013-2021. Of these, 50 received BMT (UBMT group), while 68 underwent CBT (CBT group). The primary endpoint was the 3-year overall survival (OS). There were comparable 3-year OS rates between the UBMT (51.0%, 95% confidence interval [CI]: 34.1-65.5%) and CBT (46.2%, 95% CI: 33.2-58.1%; P = 0.60) groups. In the inverse probability of treatment weighting analysis, CBT did not show significantly improved outcomes compared with UBMT regarding the 3-year OS rate (hazard ratio 0.97 [95% CI: 0.57-1.66], P = 0.91). Thus, CBT may serve as an alternative to UBMT for patients with CMML. Further research is necessary to optimise transplantation strategies and enhance outcomes in patients with CMML undergoing CBT.

Efficacy of Autologous Stem Cell Transplantation for Myeloma Patients with Suboptimal Response: A Multicenter Retrospective Analysis.

Autologous stem cell transplantation (ASCT) is the standard of care for myeloma patients who achieve partial response (PR) or better after induction therapy. However, its clinical significance in patients with suboptimal response (SR) before ASCT, including stable disease (SD) and progressive disease (PD), has not been established. Additionally, functional high-risk, including SR and early PD within 12 months, was a poor prognostic factor up to now. This study aimed to evaluate the efficacy of ASCT in myeloma patients with SR in the novel agent era. This multicenter retrospective study was conducted using the Transplant Registry Unified Management Program database of the Japanese Society of Transplantation and Cellular Therapy and included 3898 transplantation-eligible patients with newly diagnosed multiple myeloma who underwent ASCT between 2007 and 2020 and were followed up until 2021. The SR rate was 4.7%, including 1.7% with PD. In survival time analysis for overall cases, a significant difference in PFS between the very good partial response (VGPR) and PR groups was observed, whereas there was no significant difference in overall survival (OS) between the VGPR and PR groups. Additionally, there was no significant difference in OS or PFS between the PR and SD groups. Therefore, we focused on the PR, SD, and PD groups, as the purpose of this retrospective study was to investigate the clinical significance of ASCT in patients with SR compared with those with PR. The median patient age was 60 years (range, 30 to 77 years). In total, 1605 (97.4%) patients received bortezomib, 561 (38.2%) received an immunomodulatory drug (ImiD), and 512 (34.9%) received both bortezomib and an ImiD. A total of 558 patients (38.0%) received reinduction therapy. There were 229 patients (37.7%) with high-risk cytogenetics (HRCA). With a median follow-up of 31.7 months, there was a significant difference in 30-month OS rates among the PR, SD, and PD groups (86.3%, 78.5%, and 39.4%, respectively; P <.001). OS was significantly shorter in the SD group compared to the PR group among the patients with HRCA (P < .001) and patients treated with reinduction therapy (P = .013). In the PD group, the 30-month OS and PFS rates were 39.4% and 17.9%, respectively. Finally, early PD within 12 months after ASCT was predictive of short OS, whereas OS without early PD even in the PD group was similar to that in the SD and PR groups. In conclusion, OS in the SR group was not always short, but SR in the HRCA and the reinduction therapy groups was predictive of short OS, so that therapeutic alternatives to ASCT are needed. OS in the PD group was significantly short, but ASCT improved clinical outcomes when early PD did not occur even in the PD group.