Clinical and Epidemiological Characteristics of Multiple Myeloma (MM): Comparison Between Hematopoietic Stem Cell Transplantation (HSCT) and Conventional Chemotherapy,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4166-4166
Author(s):  
Gemma Ramirez ◽  
Consuelo Gonzalez Garcia ◽  
Ma Sol Durán ◽  
Javier De La Rubia ◽  
Alfons Soler ◽  
...  

Abstract Abstract 4166 INTRODUCTION: The purpose of this epidemiological retrospective study was to describe the natural history, clinical features, treatment and outcome of a wide population of multiple myeloma (MM) patients during a 2-year period. MATERIALS AND METHODS: Data from 338 patients' files from 37 Spanish centers were collected during 2009. Included patients had ISS stage II-III MM and started first line treatment according to daily practice between Sep'03-Aug'05. Response rate (RR) following IMWG criteria and survival from diagnosis are analyzed in patients either with or without hematopoietic stem cell transplantation (HSCT). Because immunotechniques were not always available back then, stringent complete response is categorized as complete response (CR) and very good partial response as partial response (PR). Statistics on survival are calculated using univarite Cox analyses, and Chi-square and Fisher exact test are used for categorical results; valid percentages are presented. RESULTS: Patients had a median of 66 (21–88) years of age at the time of diagnosis, good to moderate ECOG performance status (0–1, 50%; 2, 25%), and 1:1 ratio male:female. Besides staging II (42%) or III (58%) MM, most (95%) exhibited secretory disease, and bone lesions were common (73%). Anemia (hemoglobin <12 g/dl) was present initially in 80% of patients, hypercalcemia (calcium level ≥11 mg/dl) in 26%, and a serum creatinine level of 2 mg/dl or more in 27%. Of the 167 candidates to HSCT, 39 patients did not receive the therapy, mainly due to progression after induction (n=12), patient's decision (n=6), HSC mobilization failure (n=4), or death (n=4). Reasons for not being HSCT candidate included older age (n=112) and concomitant diseases (n=12). Table 1 resumes treatment regimens, efficacy, toxicity and survival of transplanted (T) and non-transplanted (NT) cohorts. Indution mainly consisted of conventional chemotherapy as new anti-myeloma therapies were not available during the study period. Most patients (93%) undergoing HSCT had melphalan conditioning; subsequent maintenance was given to 61 patients: interferon (75%), prednisone+/−interferon (10%), thalidomide (5%), and bortezomib (3%). Only 35 patients (9 in the T cohort) were given a second line of treatment. Objective RR (ORR=CR+PR) was higher in T than NT patients (95% vs 53%), even when both received similar chemotherapy combination, VBDA/VBMCP (94% vs 71%). When compared to this regimen, MP and VAD were significantly less effective in NT patients (ORR, 50% and 39%). Toxicity was manageable with few severe hematological events, more oftenly occurring after polychemotherapy administration. Particularly, groups of patients taking alkylator-containing regimens (either MP or VBDA/VBMCP) presented relatively higher frequency of drug-related events (46% in each group) than VAD (25%). Global median survival was 50 months (IC95%, 43– 57) and 3-year survival rate was 64% (IC95%, 57–69). In accordance to the greater efficacy, superior 3-year survival rate was achieved when receiving HSCT (85% vs 52%; p<0.001). CONCLUSION: Results of this Spanish nation-wide epidemiological study confirmed previous findings in other countries (Kyle, 2003; Conte, 2007). As expected, efficacy varied depending on patient's characteristics and treatment. No safety issues were noted. Survival rate was enhanced by HSCT. Further reports on the outcomes sorted by treatment regimen, as well as potential prognostic factors, will be presented. Disclosures: López: Celgene: Employment. Baquero:Celgene: Employment.

2020 ◽  
Vol 22 (2) ◽  
pp. 126-132
Author(s):  
Nikita E. Mochkin ◽  
Vladislav O. Sarzhevskiy ◽  
Julia N. Dubinina ◽  
Elena G. Smirnova ◽  
Denis A. Fedorenko ◽  
...  

Aim. To assess the long-term results of high-dose chemotherapy following autologous hematopoietic stem cell transplantation (autoHSCT) for multiple myeloma (MM) in the real setting and influence of different factors on the results. Materials and methods. From 2006 till 2018 in Pirogovs Center were performed 205 autoHSCT for patients with MM, aged between 3172 years (median 55). 55 (26.8%) autoHSCT were tandem. The study population consisted of 45% men and 55% women. Median follow up was 75 months. For the majority of patients autoHSCT was performed after achieving at least partial response according to the IMWG criteria. For less than 9% patients, autoHSCT was done for chemo refractory disease as a salvage therapy. Most of the patients 179 (87.4%) were treated using melphalan-based conditioning regimens (140 or 200 mg/m2). Initial staging according to ISS was done for less than 30% and to R-ISS less than 5% patients. No transplant-related mortality till D + 100 was registered. 186 patients were included in the final analysis. Results. The 5-year OS and PFS were 73% and 34%, respectively, that corresponds with international data. For patients, younger than 60, 5-year OS was 82%; for patients older than 60, it was 49% (p0.05). For tandem autoHSCT, 5-year PFS was 44%; for single autoHSCT 26% (p0.05). 5-year PFS after autoHSCT was significantly higher in patients with complete and stringent complete response after autoHSCT (44%) in comparison with the group with partial and very good partial response (77%). Sex, response before and after autoHSCT, immunomodulatory drugs in induction, number of prior lines of induction therapy, conditioning regimen and maintenance therapy had no influence on OS. PFS had the same tendencies, except tumor response after autoHSCT. Conclusion. In a real setting, we recommend tandem autoHSCT for all eligible patients with chemosensitive disease, despite the depth of response and induction therapy. Patients younger than 60 and patients with complete of greater response after autoHSCT, benefit from the autoHSCT most. Implementation of total cytogenetic testing according to the R-ISS is of a great value for further development of autoHSCT for MM in Russia.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4635-4635
Author(s):  
A. Samer Al-Homsi ◽  
Marlee Muilenburg ◽  
Kelli Cole ◽  
Muneer H. Abidi ◽  
Stephanie F. Williams

Abstract High-dose melphalan (M) followed by autologous hematopoietic stem cell transplantation (AHSCT) remains the standard treatment for multiple myeloma in eligible patients, even in the era of novel agents. However, the majority of patients ultimately relapse and succumb to their disease. Several studies have explored integrating novel agents into the conditioning regimen prior to AHSCT in order to improve complete remission rates and ultimately overall survival. We aimed to assess the feasibility of adding bendamustine (B) and carfilzomib (C) to melphalan (BCM) and performed a phase I dose escalation study. Thirteen patients were enrolled between June 2014 and June 2016. All patients received C at a fixed dose (20 mg/m2) on days (d) -29, -28, -22, -21, -15, -14. The conditioning regimen and doses administered for each cohort were as described in the table below. Due to excessive toxicity, the study was amended after the first 6 patients. Per oversight of a data safety monitoring board, the dose of M was reduced to 140 mg/m2 and C dose on d +6 was omitted. Median age was 58 years (39-68). There were 8 males and 5 females. Performance status was ≥ 80% in all patients. Per the International Staging System (ISS), 3 patients had stage I disease, 5 had stage II, 4 had stage III, and 1 had unknown staging. Three patients had high-risk cytogenetics: 2 with t(4;14) and 1 with deletion 17p. Three patients had received prior AHSCT. Disease status prior to study treatment was stable disease (SD) (n=2), partial response (PR) (n=8), or very good partial response (VGPR) (n=3). Median CD34+ cell dose was 3.24x106/kg (2.23-6.92x106). Median follow-up was 14.2 months (1-24.5). Median time to neutrophil engraftment was 12 d (11-15). One patient died before achieving platelet engraftment. For the remaining patients, median time to platelet engraftment was 16 d (12-20). Non-hematologic toxicities included grade 3 acute mucositis (n=1), lower GI complications (n=6), electrolyte disturbances (n=6), transaminase elevation (n=1) renal insufficiency (n=1), pulmonary edema (n=1), prolonged QTc (n=1), atrial fibrillation (n=1), and elevated troponin (n=1) and grade 4 acute sepsis (n=2), resulting in 1 death in cohort 2 on d +44. Seven patients went on to receive maintenance therapy: 3 with bortezomib, 3 with lenalidomide, and 1 with lenalidomide, dexamethasone, and C. Post-transplant disease status was assessed per protocol by SPEP, SPIF, and serum free light chains and light chain ratio. Nine patients were evaluable on d +100. One patient had SD, 6 had VGPR, and 2 had complete response (CR). Six out of 7 (86%) evaluable patients on d +365 remain disease progression-free. In summary, BCM conditioning prior to AHSCT at the doses described in cohort 3b seems feasible with manageable toxicities. Five additional patients are being enrolled at the same dose level. Table Table. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 93 (7) ◽  
pp. 778-784
Author(s):  
Maiia V. Firsova ◽  
Larisa P. Mendeleeva ◽  
Elena N. Parovichnikova ◽  
Maksim V. Solovev ◽  
Larisa A. Kuzmina ◽  
...  

Aim. To analyze the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a related HLA-identical donor in patients with multiple myeloma (MM). Materials and methods. From 2013 to 2018, the study included 8 patients (6 men, 2 women) aged from 27 to 55 years (median 39 years) with MM who underwent allo-HSCT from a related HLA-identical donor (7 patients after auto-HSCT, in 1 case without previous auto-transplantation). All patients required 2 or more lines of induction therapy, while the achieved antitumor effect was unstable. Before allo-HSCT, complete and very good partial remission was determined in isolated cases, in 4 patients the response was regarded as partial remission, stabilization in 1 observation, progression in 1 patient. All patients underwent reduced intensity conditioning (fludarabine 30 mg/m2 6 days + busulfan 4 mg/kg 2 days). Immunosuppressive therapy included the administration of antithymocyte globulin and post-transplant cyclophosphamide. Results. Severe acute GVHD (grade 34) was observed in 3 (37.5%) cases, which resulted in death in 1 case. A stable antitumor response was achieved in 5 (62.5%) patients, complete remission lasts for 2986 months after allo-HSCT. Specific therapy for these patients is not carried out. The 7-year progression-free survival rate was 75%, the 7-year overall survival rate was 84%, with a median follow-up of 65 months. The transplant-related mortality was 12.5%. Conclusion. Allo-HSCT is considered as an alternative method of therapy for young patients with aggressive MM. Allo-HSCT in MM in some cases leads to long-term immunological control of the tumor.


2020 ◽  
Vol 09 (04) ◽  
pp. 233-235
Author(s):  
Rahul Naithani ◽  
Nitin Dayal ◽  
Reeta Rai

Abstract Introduction Multiple myeloma (MM) in very young patients is uncommon, and no treatment guidelines exist for these patients. Patients and Methods We performed a retrospective analysis of five very young myeloma patients who underwent tandem autologous hematopoietic stem cell transplantation (HSCT). Results The median age was 37 years (range = 34–40 years). A median of two leukapheresis was performed (range = 1–4). The median number of hematopoietic stem cells collected was 5.4 × 106/kg (4.4–8.2 × 106/kg). During first transplant, four patients received melphalan of 200 mg/m2 and one patient received melphalan of 140 mg/m2 (due to renal failure) as conditioning regimen. Second transplant conditioning was melphalan of 200 mg/m2 for one patient and melphalan of 140 mg/m2 for remaining four patients. Two patients were in complete remission, and two were in very good partial remission and one patient progressed to active disease at the time of tandem autologous bone marrow transplant. All patients developed significant mucositis. Neutrophil and platelet recovery was longer in tandem autologous hematopoietic stem cell transplant. More viral infections were seen in tandem transplant. Day 30 and day 100 mortality was nil. Conclusion We present data on tandem autologous HSCTs in very young patients with MM in India. Responses continued to improve in this small series.


Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2684-2691 ◽  
Author(s):  
Sergio Giralt ◽  
William Bensinger ◽  
Mark Goodman ◽  
Donald Podoloff ◽  
Janet Eary ◽  
...  

Abstract Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation. (Blood. 2003;102:2684-2691)


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