Outcome of Patients With Nonsecretory Multiple Myeloma After Autologous Hematopoietic Stem Cell Transplantation.

INTRODUCTION: Fewer than 5% of patients have nonsecretory multiple myeloma (NSM), which is characterized by the absence of monoclonal protein in immunofixation in serum and urine. There are limited data on the outcome of NSM after autologous hematopoietic stem cell transplantation (auto-HCT). PATIENTS AND METHODS: Between 1988 and December 2010, we identified 31 patients with NSM, and compared their outcome with 124 patients with secretory myeloma (SM) who were matched for age, disease stage, year of auto-HCT, and disease status and received auto-HCT at our institution. The primary end points were time to progression (TTP), progression-free survival (PFS), and overall survival (OS). RESULTS: Nonrelapse mortality at 4 years was 4% and 4% in the NSM and SM patients, respectively (P = .612). Median follow-up was 102 and 74 months for NSM and SM patients, respectively. Median PFS was 37 (95% confidence interval [CI], 12-62) and 22 (95% CI, 18-26) months for NSM and SM patients, respectively (P = .527). Median OS was 51 (95% CI, 7-95) and 73 (95% CI, 59-86) months for NSM and SM patients, respectively (P = .740). In multivariate analyses, age >55 years, and relapsed disease were associated with a shorter TTP. Similarly, age >55 years, and relapsed or refractory disease at the time of auto-HCT were associated with a shorter OS. CONCLUSION: Auto-HCT is associated with durable remission in NSM. There was no significant difference in transplant-related mortality, TTP, and PFS in patients with NSM compared with patients with SM after high-dose therapy and auto-HCT.

Predictors of prolonged survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma.

A total of 149 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with myeloablative (MAC; n = 38) or reduced-intensity conditioning (RIC; n = 110) regimens at MD Anderson Cancer Center were evaluated. Of the total, 120 (81%) patients had relapsed or had refractory disease. Median age of MM patients was 50 (28-70) years with a followup time of 28.5 (3-164) months. The 100-day and 5-year treatment related mortality (TRM) rates were 17% and 47%, respectively. TRM was significantly lower with RIC regimens (13%) vs. 29% for MAC at 100 days (P = 0.012). The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) was 35% and chronic GVHD was 46%. PFS and OS at 5 years were 15% and 21%, respectively. In multivariate analysis, allo-HCT for primary remission consolidation was associated with longer PFS (HR 0.35; 95% CI, 0.18-0.67) and OS (HR 0.29; 95% CI 0.15-0.55), while absence of high-risk cytogenetics was associated with longer PFS only (HR 0.59; 95% CI 0.37-0.95). We observe that TRM has decreased with the use of RIC regimens, and long-term disease control can be expected in a subset of MM patients undergoing allo-HCT. Further studies should be conducted in carefully designed clinical trials in this patient population.

Durable responses after donor lymphocyte infusion for patients with residual multiple myeloma following non-myeloablative allogeneic stem cell transplant.

The role of donor lymphocyte infusion (DLI) in mediating the graft-versus-myeloma (GvM) effect after allogeneic hematopoietic stem cell transplant (allo-HCT) is not clearly defined. We evaluated the safety and utility of DLI in patients with either persistent or recurrent multiple myeloma (MM) after allo-HCT. Twenty-three patients with MM received DLI after allo-HCT at the University of Texas M. D. Anderson Cancer Center between July 1996 and June 2008. Eight patients received preemptive DLI for residual disease (RD) while 15 patients received DLI for the treatment of recurrent or progressive disease (PD). We evaluated the response to DLI and the factors that may predict a response. Median DLI dose was 3.3 × 10(7) CD3 + cells (range 0.5-14.8 × 10(7)). Grade II-IV acute graft-versus-host disease (GvHD) was seen in five patients (22%). Median follow-up in surviving patients was 24 months. Five of 23 patients (22%) achieved a complete or a very good partial response (two CR, three VGPR), while eight patients (34%) had stable disease (SD) after the DLI. Patients who received DLI for RD had a higher response rate (≥ VGPR 50% vs. 7%, p = 0.03), a longer overall survival (28.3 vs. 7.6 months, p = 0.03) and a trend toward longer progression-free survival (11.9 vs. 5.2 months, p = 0.1). In this largest single institution study, we conclude that the use of preemptive, non-manipulated DLI for RD after reduced-intensity conditioning allo-HCT is encouraging, and it was associated with a higher response rate and a longer overall survival when given preemptively. The role of DLI needs to be further explored in prospective clinical trials.

Durable remission with salvage second autotransplants in patients with multiple myeloma.

BACKGROUND: High-dose chemotherapy with autologous hematopoietic cell transplant (auto-HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto-HCT for relapsed patients, particularly in the era of novel therapeutics, is not well defined. METHODS: The authors performed a retrospective analysis of all 44 myeloma patients (24 men, 20 women) who received a second auto-HCT as salvage between January 3, 1992 and November 4, 2008 at The University of Texas MD Anderson Cancer Center. RESULTS: Median interval between the first and salvage auto-HCT was 30 months (range, 2-78 months). Median age at salvage HCT was 54 years (range, 38-73 years), and median number of salvage treatment regimens was 2 (range, 0-5). Eleven (25%) patients had high-risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto-HCT. Ten patients (23%) experienced grade 3 or higher nonhematologic toxicity after the salvage auto-HCT. One patient died within 100 days, for a treatment-related mortality of 2%. Best responses after salvage chemotherapy + salvage auto-HCT were as follows: complete response (CR) + near CR, 11%; partial response, 79%; overall response rate, 90%. Eighteen (41%) patients received post auto-HCT maintenance therapy. Median follow-up from salvage HCT was 41 months. Kaplan-Meier estimates of median progression-free survival (PFS) and overall survival (OS) from time of salvage auto-HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression after first auto-HCT, greater number of prior therapies, African American race, and immunoglobulin G subtype were significantly associated with worse OS. CONCLUSIONS: In selected myeloma patients, a second auto-HCT for salvage therapy is well tolerated, with acceptable toxicity. The overall response rate and PFS are comparable to other salvage regimens.

Feasibility of autologous hematopoietic stem cell transplant in patients aged ≥70 years with multiple myeloma.

Abstract We retrospectively analyzed the outcomes of all consecutive patients with myeloma (n = 84) aged ≥70 years who had received autologous hematopoietic stem cell transplant (auto HCT) between July 1999 and June 2010 at our institution. The median age at auto HCT was 72 years, the median number of prior therapies was 2.5 and the median time from diagnosis to auto HCT was 10.2 months. The conditioning regimen consisted of melphalan at 140 mg/m(2) in 10%, 180 mg/m(2) in 25% and 200 mg/m(2) in 65% of patients. The day-100 non-relapse mortality was 3%. The overall response rate at day 100 was 85% (complete response 18%, very good partial response 12%, partial response 55%). After a median follow-up of 25 months among surviving patients, the estimated progression-free survival and overall survival at 5 years were 27% and 67%, respectively. The incidence of grade II-IV toxicity, response rate and survival were similar across three melphalan dose levels. These results indicate that high-dose melphalan plus auto HCT is safe and feasible for patients with multiple myeloma aged ≥70 years and age alone should not be an exclusion criterion for auto HCT.

The outcome of IgD myeloma after autologous hematopoietic stem cell transplantation is similar to other Ig subtypes.

IgD myeloma is a rare subtype of myeloma that is associated with an aggressive course, resistance to chemotherapy, and a poor outcome. We identified 17 patients with IgD myeloma, who received a hematopoietic stem cell transplantation (HCT) at our institution between August 1988 and June 2008. Fifteen of these 17 patients underwent an autologous (auto) HCT. Complete responses (CRs) were seen in 6 of 15 (40%) patients; three converted from partial response to CR, two from minimal response to CR, and one from very good partial response to CR. The overall response rate after auto HCT was 86% (13 of 15). Kaplan-Meiers estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 38% and 64%, respectively. Median PFS and OS were 18 and 45 months, respectively. These results were comparable with patients receiving autologous HCT for other Ig subtypes of myeloma.

Reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed multiple myeloma.

Despite recent advances, multiple myeloma (MM) remains incurable, and most patients eventually develop progressive disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a potentially curative option in 10%-20% of patients with relapsed or refractory disease. We evaluated the outcome of patients undergoing allo-HSCT with reduced-intensity conditioning (RIC) for relapsed and/or refractory MM at our institution. The study cohort included 51 patients with heavily pretreated, relapsed MM who underwent RIC allo-HSCT between 1996 and 2006. The median time from diagnosis to allo-HSCT was 34 months, and median follow-up in surviving patients was 27 months (range, 3-98 months). Cumulative transplantation-related mortality at 1 year was 25%. Progression-free survival (PFS) and overall survival (OS) at 2 years were 19% and 32%, respectively. The incidences of grade II-IV acute and chronic graft-versus-host disease were 27% and 47%, respectively. At the time of this analysis, 12 patients (24%) were alive, 7 of whom (14%) were in remission for up to 6 years after allo-HSCT. A lower beta2 microglobulin level (<3.3) and previous autologous HSCT were predictive of lower nonrelapse mortality and longer PFS and OS. Our findings indicate that allo-HSCT with RIC is associated with acceptable toxicity and durable remission and survival in relapsed or refractory MM. The use of RIC allo-HSCT earlier in the course of the disease may offer the greatest benefit.

Outcome of allogeneic hematopoietic stem cell transplantation in patients with low left ventricular ejection fraction.

A high risk of regimen-related toxicity with allogeneic hematopoietic stem cell transplantation (allo-HSCT) limits this potentially curative treatment for patients with a left ventricular ejection fraction (LVEF) of > or =50%. We evaluated the frequency of cardiac complications and 100-day nonrelapse mortality (NRM) in 56 patients with a LVEF of < or =45%, who received allo HCT at our institution. The results were retrospectively compared with a matched control group with LVEF of > or =50%, which received an allogeneic stem cell transplantation (allo-SCT). After a median follow-up of 29 months in the study group, grade > or =2 cardiac complications were seen in 7 of 56 (12.5%) patients and cumulative incidence of 100-day NRM was 12.5% with no deaths from cardiac causes. In contrast, after a median follow-up of 49 months in the control group, grade >2 cardiac complications were seen in 19 of 161 patients (11.8%; P = 1.00) and cumulative incidence of 100-day NRM was 14.9% (P = .82). The presence of at least 1 of the 7 pretransplant cardiac risk factors (past history of smoking, hypertension, hyperlipidemia, coronary artery disease, arrhythmia, prior myocardial infarction, and congestive heart failure) was associated with a higher cardiac complication rate in the study group (P = .03). In conclusion, selected patients with a LVEF of < or =45% can safely receive allo-HCT without a significant increase in cardiac toxicity or NRM.