Introduction Cyclophosphamide–bortezomib–dexamethasone (CyBorD) is considered a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (mm). It has not been prospectively compared with bortezomib–dexamethasone (Bor-Dex). We aimed to compare the efficacy of CyBorD and Bor-Dex induction in transplant-eligible patients. Methods In a retrospective observational study at a single tertiary centre, all patients with transplant-eligible mm who received induction with CyBorD or Bor-Dex between March 2008 and April 2016 were enrolled. Progression-free survival (pfs), response, and stem-cell collection for a first autologous stem-cell transplantation (ahsct) were compared. Results Of 155 patients enrolled, 78 (50.3%) had received CyBorD, and 77 (49.7%), Bor-Dex. The patients in the Bor-Dex cohort were younger than those in the CyBorD cohort (median: 57 years vs. 62 years; p = 0.0002) and more likely to have had treatment held, reduced, or discontinued (26% vs. 14.5%, p = 0.11). The stem-cell mobilization regimen for both cohorts was predominantly cyclophosphamide and granulocyte colony–stimulating factor (gcsf). Plerixafor was used more often for the CyBorD cohort (p = 0.009), and more collection failures occurred in the CyBorD cohort (p = 0.08). In patients receiving Bor-Dex, more cells were collected (9.9×106 cells/kg vs. 7.7×106cells/kg, p = 0.007). At day +100, a very good partial response or better was achieved in 75% of the CyBorD cohort and in 73% of the Bor-Dex cohort (p = 0.77). Median pfs was 3.2 years in the Bor-Dex cohort and 3.7 years in the CyBorD cohort (p = 0.56). Conclusions Overall efficacy was similar in our patients receiving CyBorD and Bor-Dex. After ahsct, no difference in depth of response or pfs was observed. Cyclophosphamide–gcsf seems to increase collection failures and hospitalizations in patients receiving CyBorD. Prospective studies are required to examine that relationship.
Background: Local irradiation results in long-term control and even cure of solitary plasmacytomas, but traditional total body irradiation (TBI) elicits excessive normal tissue toxicity limiting dose escalation for multiple myeloma patients. Intensity modulated radiation, a more targeted form of irradiation to the entire marrow (total marrow irradiation or TMI), delivers up to 70% less radiation to adjacent normal tissues compared to standard TBI approaches. We postulate that TMI will allow delivery of higher doses of radiation to the marrow which might improve outcome of patients with myeloma. Objectives: Primary outcomes are to determine safety and maximum tolerated dose (MTD) of TMI. A secondary outcome was time to next treatment (TTNT). Methods: This is an ongoing dose-escalation study of TMI as sole conditioning for salvage autologous hematopoietic stemcell transplant (TMI-SCT) in radiation-naïve myeloma patients failing a first-line melphalan-aHSCT (Mel-SCT). Measurable myeloma and stored CD34 + cells (≥2.5 × 10 6 /kg) were study prerequisite. TMI doses were given twice daily starting with 14 Gy, then one fraction of 2 Gy was added to successive cohorts of three patients. Acute and long-term toxicity were graded using Bearman scale and LENT-SOMA respectively. Results: Fourteen patients were transplanted between January-2010 and May-2017. Three patients received 14 Gy, 16 Gy, 18 Gy and 20 Gy. One patient received 22 Gy and one patient scheduled for 22 Gy received 19.8 Gy because of early mucositis. Median age at TMI was 59.5 years and median time between Mel-SCT and TMI-SCT was 2.9 years. Increase in TMI dose was associated with mucositis worsening (P < .01), but not with narcotics usage, or fever. Xerostomia was the most common long-term toxicity observed, and it was graded LENT-SOMA ≥ 2 in 63.6%, 38.5% and 25% of the patients at D100, 6 months and 12 months post-TMI respectively. There was no difference in length of hospitalization, neutrophil engraft-ment, and incidence of acute toxicity between TMI-SCT and Mel-SCT. There was no difference in myeloma response after Mel-SCT compared to after TMI-SCT (Table 1). Conclusion: When compared to a well-established conditioning, TMI was safe and disease control was encouraging. MTD was not reached. Further increase in TMI dose and longer follow-up are needed for better investigation.
Introduction The use of allogeneic stem cell transplantation (Allo-SCT) in patients with multiple myeloma (MM) remains controversial, but it offers prolonged disease free survival in some patients. It is unclear which patients should undergo Allo-SCT, what conditioning regimen should be used, and what the timing of the transplant should be in the course of the disease. Therefore, we sought to contribute our center's experience to the growing body of literature. Methods We performed a retrospective observational cohort study of all patients who underwent Allo-SCT for multiple myeloma at our center between January 1, 1992 and May 31, 2016. Categorical variables were compared using Pearson's chi-square test and the Kaplan-Meier method was used for the overall survival curves. Results Thirty-four patients underwent Allo-SCT for multiple myeloma and were included in this analysis. The median age was 40 years and 21 (62%) were male. Nineteen patients (56%) underwent Allo-SCT as upfront therapy, 1 (3%) underwent tandem autologous stem cell transplant (auto-SCT) followed by Allo-SCT, and 14 (41%) had salvage Allo-SCT at the time of relapse. Twenty-four (70.5%) patients had a matched related donor, 1 (3%) had a mis-matched related donor, 8 (23.5%) had matched unrelated donor and matching in 1 (3%) was not available. Myeloablative conditioning was given in 18 patients (52.9%) and non-myeloablative conditioning in 13 (38.2%) with 3 (8.8%) missing. The conditioning regimens included: 5 (15%) Flu-Mel, 7(20.6%) Flu-Bu, 13 (38%) Bu-Cy ± TBI, 6 (17.6%) MelVPTBI, and 3 (8.8%) were missing. Median overall survival (OS) for all patients was 72.5 months from diagnosis (figure 1) and 26.5 months from the time of Allo-SCT. For the 19 patients who had upfront Allo-SCT, median OS from diagnosis was 7.4 years compared to 5.3 years for those having salvage Allo-SCT (figure 2). However, in the upfront group 6 (32%) were alive 10 years post Allo-SCT and the survival curve reaches plateau, whereas in the salvage group, no patient was alive after 8 years post Allo-SCT. There was no difference in median survival between myeloablative and non myeloablative conditioning (2.9 versus 1.33 years, p=0.925). There have been 20 deaths in our cohort (59%); 5 (14.7%) from transplant related mortality within 1 year, 9 (26.5%) from disease progression, and 6 (17.6%) transplanted remotely whose cause of death is unknown. Conclusions Our data suggest that Allo-SCT offers prolonged disease free survival in some patients. In our small cohort, a greater proportion of patients undergoing upfront Allo-SCT achieved long term survival, raising the possibility that this group of patients may benefit more from Allo-SCT. Further prospective studies are needed to clarify the role of Allo-SCT in MM. Disclosures Kew: Celgene: Honoraria. McCurdy:Celgene: Honoraria.
Introduction Cyclophosphamide, bortezomib, and dexamethasone (CyBor-D) is considered a standard induction regimen for transplant eligible patients with newly diagnosed multiple myeloma (MM) based primarily on phase 2 data. It has not been directly compared to bortezomib and dexamethasone (Bor-Dex) alone. Therefore, we sought to compare the efficacy CyBor-D and Bor-Dex induction in transplant eligible patients treated at a tertiary care center. Methods A retrospective observational study was performed from a single tertiary care center between January 1, 2008 and April 30, 2016. All transplant eligible patients with MM who received induction chemotherapy with CyBor-D or Bor-Dex and were included. The primary outcome was progression free survival (PFS). Secondary outcomes were response to induction, toxicity, stem cell collection yield and failures, and response to autologous stem cell transplant (autoSCT). Continuous variables were reported as median and compared using Mann-Whitney test. Categorical variables were compared using Pearson's chi-square test. PFS was estimated with Kaplan-Meier. Results One hundred and fifty nine patients were included, 82 (51.6%) treated with CyBor-D and 77 (48.4%) treated with Bor-Dex. The relative proportion of patients treated with CyBor-D increased annually: 1/23 (4%) in 2012, 20/30 (66%) in 2013, 33/34 (97%) in 2014, and 28/28 (100%) in 2015. Patient demographics and disease characteristics were similar between all groups for sex, subtype of MM and stage by the International Staging System. The Bor-Dex group was significantly younger than the CyBor-D group (mean age 56 vs. 61 years, p < 0.001). Median number of cycles was the same for both groups (4, p= 0.73); however, the Bor-Dex group was more likely to have treatment held, reduced or discontinued than the CyBor-D group (19.7% vs. 6.4%, p=0.017). The overall response rate (ORR) was similar between both groups, 88.5% for CyBor-D and 82.7% for Bor-Dex (p=0.36), but patients treated with CyBor-D had deeper responses to induction with 57.5% achieving ≥VGPR whereas 38.7% in the Bor-Dex group achieved ≥ VGPR (p=0.02). The stem cell mobilization regimen was predominantly Cyclophosphamide and GCSF for both groups. Plerixafor use was more common in the CyBor-D cohort, 14.6% vs. 1.3% in Bor-Dex (p=0.002), and there were more collection failures in the CyBor-D group compared to Bor-Dex (6.1% vs. 0%, p=0.03). The median number of CD34 cells collected was higher in the Bor-Dex compared to CyBor-D (9.88 x 106 cells/kg vs. 7.66 x 106cells/kg, p=0.004), however median collection days was similar (1 in both groups, p=0.175). The mobilization toxicity was similar between both groups with a trend towards increased hospitalizations in the CyBor-D group (26% vs. 14%, p=0.075). The conditioning regimen was the same in both groups, predominantly Melphalan 200 mg/m2. Day 100 response was similar, with 76.7% of CyBor-D patients achieving ≥ VGPR vs. 71.21% for Bor-Dex (p= 0.25). The median PFS was 36.5 months in the Bor-Dex group and not yet reached in the CyBor-D group, due to shorter follow up time. However, the percentage of patients free from relapse was similar at 1 year (92.8% for CyBorD vs 98.7% for Bor-Dex) and at 2 years (69.4% for CyBor-D vs 72.9% for Bor-Dex). Conclusions CyBor-D and Bor-Dex appear to have similar overall efficacy for newly diagnosed transplant eligible patients with multiple myeloma in our cohort. CyBor-D was associated with deeper response to induction, but after autoSCT there was no difference in the depth of response between the two cohorts. Longer follow up is required to detect if the deeper response to induction with CyBor-D leads to differences in PFS. When used with Cyclophosphamide-GCSF mobilization, CyBor-D appears to result in more collection failures and a trend towards increased hospitalizations. Further prospective studies are required to examine this relationship. Disclosures Kew: Celgene: Honoraria. McCurdy:Celgene: Honoraria.
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