Novel Agents for Initial Therapy of Multiple Myeloma: Comparable Results with Continued Initial Therapy and Delayed Transplantation at Relapse Versus Early Transplantation.
Abstract Abstract 956 Background: Autologous SCT has been an integral part of myeloma therapy since randomized trials demonstrated improved survival for SCT compared to conventional therapy. However, the conventional treatment of MM has changed with the introduction of novel therapies such as IMiDs and there is an increasing trend towards delaying SCT. While trials in the pre-novel agent area have shown equivalent outcomes with early or delayed SCT, it is not clear if this holds true with novel agent induction. Patients and methods: We reviewed the outcome of patients seen at Mayo Clinic between 2001 and 2008, who received initial therapy with thalidomide-dexamethasone (TD) or lenalidomide-dexamethasone (LD) (n=410). All patients in whom a stem cell harvest was attempted (started on growth factor irrespective of collection success; n=292, 71%) were included as a method to identify transplant eligible patients. Patients undergoing SCT within 12 months of diagnosis and in whom the SCT was performed within 2 months of stem cell harvest were considered in the early SCT group vs. delayed SCT for the remaining patients irrespective of whether an SCT was actually done (immediate vs. collect and store approach). Variables were compared between the groups using a chi-square or t-test as appropriate. Survival curves were generated using Kaplan Meier method and compared using log rank test. Results: Among the 292 transplant eligible patients, 125 (43%) received TD and 167 (57%) received LD as initial therapy. An early SCT approach was undertaken in 174 patients 60%, with the remaining 118 in the delayed group, 46 of whom have been transplanted to date. The median estimated follow up for the entire group was 54 months from diagnosis, 52 and 61 months respectively for the early and delayed groups. The median estimated time to SCT was 5.3 months among the early group compared to 39 months in the delayed group COMMENTS/* MERGEFORMAT . 83 (66%) patients receiving TD had an early SCT compared to 91 (55%) patients in the LD group; p =0.04. At baseline, the groups were comparable for age and gender. The median overall survival from diagnosis was 86 months for the early SCT compared to NR for the late SCT; P=0.3. The median OS was similar between the Early and Delayed group in the TD group (86 vs. 64 months respectively) as well as in the LD group (NR for either group; 82% vs. 86% at 4 years respectively). Conclusion: In this group of newly diagnosed patients treated with thalidomide or lenalidomide as initial therapy, an approach of continued initial therapy and delayed transplant at the time of first relapse appears comparable to upfront transplant. This is consistent with the findings of randomized trials in the setting of alkylator based initial therapies. The timing of transplant in the era of novel agents remains the top question on the mind of physicians and patients, and this is the first study to examine this very important question. The rationale governing the decision to go forward with an early SCT or delayed transplant is difficult to ascertain for any particular patient in this retrospective study. These findings should be confirmed in prospective randomized trials. Disclosures: Kumar: celgene: Research Funding; millenium: Research Funding. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Delayed neutrophil engraftment in patients receiving Daratumumab as part of their first induction regimen for multiple myeloma
B49. CRITICAL CARE: EAST OF EDEN - PREDICTING AND MEASURING OUTCOMES | August 26, 2019 | Volume: No volume available | Issue: No issue available | Pages: A3451-A3451
AbstractThe role of consolidation post autologous stem cell transplant in light chain amyloidosis is not well defined. We retrospectively identified patients who had light chain amyloidosis and underwent autologous stem cell transplant at the Mayo Clinic. Consolidation was defined as any treatment given after the day 100 evaluation post‐transplant to maintain or deepen the response. We identified 471 patients, of whom 72 (15%) received consolidation. Patients receiving consolidation had more advanced disease (Mayo 2012 stage ≥II in 67% vs 52%, P = .02), and had lower day 100 response rates (very good partial response or better: 35% vs 84%, P < .001). After consolidation, rates of very good partial response improved from 24% to 28%, and rates of complete response improved from 11% to 40%. Patients with less than very good partial response who received consolidation, had better progression‐free survival (median of 22.4 vs 8.8 months, P < .001), and the benefit was greater in those who deepened their response (median of 41 vs 8.8 months, P < .001). In patients with less than very good partial response, there was a trend for better overall survival in patients who responded to consolidation (median of 125.8 vs 74.4 months, P = .07). In patients who achieved very good partial response, or better, at day 100 post autologous stem cell transplant, consolidation did not improve progression‐free or overall survival. Consolidation after autologous stem cell transplant for light chain amyloidosis improves progression‐free survival for patients who achieve less than very good partial response.
Fifteen year overall survival rates after autologous stem cell transplantation for AL amyloidosis
Abstract In appropriately selected patients with AL amyloidosis, autologous stem cell transplant (ASCT) is an established treatment modality with excellent outcomes and decreasing transplant related mortality (TRM) over time. We report on 15‐year overall survival (OS) in 159 patients undergoing ASCT from 1996 to 2003, with median follow up of 17.1 years. Day 100 TRM was 13.2% (n = 21). The OS of ≥15 years was observed in 30% (47/159) of patients. Patients surviving ≥15 years were younger (53 vs 56 years, P = .02), less likely to have lambda as the involved light chain (62% vs 78%, P = .03) and were less likely to have heart involvement (32% vs 56%, P = .005). Median OS of patients with heart involvement vs not was 4.0 vs 11.1 years, P = .006 and actuarial 15‐year OS was 23% vs 43%, respectively. A higher proportion of patients with OS ≥15 years received full‐dose melphalan conditioning (81% vs 61%, P = .01), and achieved day 100 complete response (CR) (64% vs 24%, P < .001). Median OS amongst patients who achieved CR vs not was 19.3 vs 5.4 years, P < .001. Heart involvement, receiving full‐dose melphalan and achieving CR remained independent predictors of OS. AL amyloidosis and related complications were the cause of death in 52% of patients overall (1‐5 years post‐transplant: 81%; 5‐10 years: 62% and 10‐15 years: 55%). These results reinforce the key role of ASCT in AL amyloidosis. With improvements in TRM and more options for relapsed disease, we expect the long‐term survival post‐transplant to improve significantly in the future.
Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report
Abstract Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or ≥5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
Implementation of a patient blood management program in hematopoietic stem cell transplantation (Editorial, p. 2763)
BACKGROUNDRecipients of hematopoietic stem cell transplantation (HSCT) are among the highest consumers of allogeneic red blood cell (RBC) and platelet (PLT) components. The impact of patient blood management (PBM) efforts on HSCT recipients is poorly understood.STUDY DESIGN AND METHODSThis observational study assessed changes in blood product use and patient‐centered outcomes before and after implementing a multidisciplinary PBM program for patients undergoing HSCT at a large academic medical center. The pre‐PBM cohort was treated from January 1 through September 31, 2013; the post‐PBM cohort was treated from January 1 through September 31, 2015.RESULTSWe identified 708 patients; 284 of 352 (80.7%) in the pre‐PBM group and 225 of 356 (63.2%) in the post‐PBM group received allogeneic RBCs (p < 0.001). Median (interquartile range [IQR]) RBC volumes were higher before PBM than after PBM (3 [2‐4] units vs. 2 [1‐4] units; p = 0.004). A total of 259 of 284 pre‐PBM patients (91.2%) and 57 of 225 (25.3%) post‐PBM patients received RBC transfusions when hemoglobin levels were more than 7 g/dL (p < 0.001). The median (IQR) PLT transfusion quantities was 3 (2‐5) units for pre‐PBM patients and 2 (1‐4) units for post‐PBM patients (p < 0.001). For patients with PLT counts of more than 10 × 109/L, a total of 1219 PLT units (73.4%) were transfused before PBM and 691 units (48.8%) were transfused after PBM (p < 0.001). Estimated transfusion expenditures were reduced by $617,152 (18.3%). We noted no differences in clinical outcomes or transfusion‐related adverse events.CONCLUSIONPatient blood management implementation for HSCT recipients was associated with marked reductions in allogeneic RBC and PLT transfusions and decreased transfusion‐related costs with no detrimental impact on clinical outcomes.
Higher CD3 cell counts in apheresis collection in relation to superior survival in patients with multiple myeloma.