Multiple Myeloma Patients Treated at Academic Centers Have Improved Survival Outcomes

Abstract Background Treatment at academic cancer centers (ACs) has been associated with improved outcomes across hematologic malignancies, including acute myeloid leukemia and non-Hodgkin lymphoma. ACs offer the benefit of high treatment volume in addition to enrollment in clinical trials, involvement in post-graduate education, and expanded access to diagnostic and treatment related services. Though studies on multiple myeloma (MM) have demonstrated a survival benefit with treatment at both high-volume centers and at NCCN designated cancer centers, this is the largest study to date examining the benefit of academic centers. Methods The National Cancer Database was utilized to obtain data on patients diagnosed with MM between 2004-2017 for which data on treatment facility type was available. Using the Commission on Cancer facility categories, patients treated at ACs were compared to those treated at non-academic centers (NACs), including small and large volume community cancer centers. Demographic and treatment characteristics were compared between centers, with median overall survival (OS) assessed by Kaplan Meier. Cox regression analysis was used to asses the HR for OS by facility type, and adjusted on multivariate analysis for age, sex, race, insurance, time to treatment, and use of autologous transplant. Results Of the 179,769 MM patients available, 42.4% were treated at ACs (p<0.05). Patients treated at ACs were younger than those treated at NACs (mean age 64.7 years vs. 69.2 years, p<0.05) and patients > 75 years of age were more often treated at NACs (35.6% vs. 20.3%, p<0.05). ACs were more likely to treat Black and other minority patients, with Black patients representing 23.5% vs. 18%, and other minorities 5.6% vs. 3.6% of patients treated at ACs vs. NACs, respectively; all p<0.05. Academic centers were more likely to treat uninsured patients (6.3% vs. 4.1%), patients on Medicaid (7.9% vs. 5.5%) as well as privately insured patients (41.5% vs. 29.6%),( all p<0.05). The majority of Medicare patients were treated at NACs (60.8%), p<0.05. The time from diagnosis to treatment was longer at ACs, at 32.4 vs. 26.5 days (p<0.05), and patients were more likely to receive autologous stem cell transplant as first line treatment at ACs (6.3% vs 2.2%, p<0.05). While clinical trial data is limited in the NCDB, the majority of the 495 patients treated under a clinical trial were treated at ACs (393 vs 102, or 0.5% vs 0.1% of patients treated at ACs vs NACs, p<0.05). Median OS at ACs was significantly longer than at NACs, with median OS of 67.8 months (95% CI 66.89-68.79 months) compared to 38.6 months (95% CI 38.15-39.13 months) at NACs, p<0.05. One year OS was 75% vs 61%, 5-year OS 48% vs 33%, and 10-year OS of 22% vs 12% at ACs vs NACs, respectively; p<0.05. When adjusted for age, gender, race, insurance, time to treatment, and use of autologous transplant on Cox Regression analysis, the improvement in OS remained. Patients treated at AC had hazard ratio of 0.77 for all-cause mortality (95% CI 0.756-0.784) when referenced to NACs on multivariate analysis (p<0.05). Conclusion Patients with MM had significantly improved survival when treated at academic centers compared to all other facility types. The improvement in OS remained when controlled for available treatment and demographic features. Multiple factors, including specialized care, trial enrollment, and early access to autologous stem cell transplant may contribute to these improvements. Further investigations into the factors contributing to such disparities are required to standardize care and improve overall outcomes. Figure 1 Figure 1. Disclosures Tantravahi: CTI BioPharma: Research Funding; Novartis: Research Funding; BMS: Research Funding; Abbvie Inc.: Research Funding; Karyopharm Therapeutics Inc.: Consultancy, Honoraria, Research Funding. Sborov: SkylineDx: Consultancy; GlaxoSmithKline: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy.

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Stem Cell Transplant without Growth Factor In Multiple Myeloma: Engraftment Kinetics, Bacteremia, and Hospitalization.

Blood ◽

10.1182/blood.v116.21.3469.3469 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3469-3469

Author(s):

Morie Abraham Gertz ◽

Dennis Gastineau ◽

Martha Lacy ◽

Angela Dispenzieri ◽

Suzanne R. Hayman ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Growth Factors ◽

Growth Factor ◽

Research Funding ◽

Stem Cell Transplant ◽

The United States ◽

Median Number ◽

Autologous Stem Cell Transplant ◽

Cell Transplant

Abstract Abstract 3469 Introduction: Stem cell transplantation is important in the management of multiple myeloma. In the United States, the standard of care is administration of growth factors to accelerate neutrophil recovery after stem cell transplant. The need for growth factors after transplant has not been investigated recently. Patients: We analyzed a cohort of 166 patients at our institution who underwent autologous transplant for multiple myeloma without receiving growth factors after transplant and compared them with 498 patients who received standard filgrastim beginning on posttransplant day 5. TABLE Results: A neutrophil count of 500/μL was achieved in a median of 12.5 days in patients receiving growth factor, compared with 13.5 days in those not receiving growth factor (P<.001) Fig 1. Platelet engraftment was identical (median, 14.5 days; P=.12) in both groups, despite a lower median number of CD34+ cells infused in patients who did not receive growth factors. Incidence of nonstaphylococcal bacteremia was identical in both groups. The median hospital stay was 3.5 days shorter in the group not receiving growth factor. Bacteremia impacted platelet but not neutrophil engraftment. Figure 2 Conclusion: It is feasible and reasonable to perform autologous stem cell transplant for multiple myeloma without administering growth factors. Estimated savings would be $4,600 for each transplanted patient. Growth factor administration is not required for a safe outcome and decreases the number and severity of some of the fluid-related complications after transplant such as acute respiratory distress syndrome, allergic reactions, alveolar hemorrhage, and rarely splenic rupture. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lacy:Celgene: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

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Absolute Lymphocyte Count As Predictor of Overall Survival for Patients with Multiple Myeloma Treated with Single Autologous Stem Cell Transplant: Experience of a Single Centre,

Blood ◽

10.1182/blood.v118.21.4121.4121 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4121-4121

Author(s):

Victor H Jimenez-Zepeda ◽

Donna E. Reece ◽

Suzanne Trudel ◽

Christine Chen ◽

Norman Franke ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Lymphocyte Count ◽

Research Funding ◽

Stem Cell Transplant ◽

Plasma Cells ◽

Absolute Lymphocyte Count ◽

Autologous Stem Cell Transplant ◽

Peripheral Blood Lymphocytes ◽

Cell Transplant

Abstract Abstract 4121 Post-Autologous stem cell transplant (ASCT) studies have demonstrated that early absolute lymphocyte count (ALC) recovery is associated with prolonged survival in some hematological malignancies. Peripheral blood lymphocytes from Multiple Myeloma (MM) were shown to have direct anti-MM activity by proliferative and cytotoxic responses to autologous and allogeneic myeloma plasma cells Disclosures: Jimenez-Zepeda: J & J: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

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The Effect of Maintenance Therapy Following Salvage Autologous Stem Cell Transplant in Multiple Myeloma Patients

Blood ◽

10.1182/blood-2018-99-111379 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3439-3439

Author(s):

Brandon B. Wang ◽

Mark A. Fiala ◽

Mark A. Schroeder ◽

Tanya Wildes ◽

Armin Ghobadi ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Maintenance Therapy ◽

Board Of Directors ◽

Research Funding ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Advisory Committees ◽

The Impact

Abstract Background: In the current era, autologous stem cell transplant (ASCT) remains an effective form of treatment for patients diagnosed with multiple myeloma (MM), but it is not curative and a relapse is inevitable. A second, or salvage, ASCT provides better outcomes than conventional chemotherapy but it is infrequently used. Maintenance therapy after initial ASCT has been adopted as the standard in the US; however, there is limited data on the effects of maintenance therapy following salvage ASCT and the benefits are still unclear. Methods: We performed retrospective chart review of all patients with MM who received a second, salvage ASCT at time of first relapse at Washington University in St. Louis from 2008 to 2016. We identified two cohorts of patients, those who received maintenance therapy following salvage ASCT and those who did not. Patients who received maintenance therapy post-initial ASCT were excluded as the objective of this study was to determine the impact of maintenance post-salvage ASCT and maintenance post-initial ASCT may confound the results. Results: Sixty-five patients (who underwent second/salvage ASCT) were identified. Three were excluded from the analysis-two had treatment-related mortality following salvage ASCT and one received maintenance other than a proteasome inhibitor (PI) or an immunomodulatory drug (IMID). The maintenance cohort consisted of 31 patients, with 68% (n = 21) males and 32% (n = 10) females; the median age at salvage ASCT was 61 years (range 38-73). The no-maintenance cohort consisted of 31 patients as well with 45% (n = 14) males and 55% (n = 17) females. Their median age at salvage ASCT was 62 years (range 44-74). The characteristics of the two cohorts are summarized in Table 1. Most patients received PIs and/or IMIDs as part of their induction regimens prior to initial ASCT. All received melphalan conditioning. The response to treatment was similar between the two cohorts, with respective CR rates of 68% (n = 21) and 77% (n = 24) and median progression-free survival (PFS) of 46 months compared to 33 months. Following relapse, 16% (n = 5) of patients in the no-maintenance cohort proceeded directly to salvage ASCT without re-induction. All other patients received re-induction, mostly with PIs and/or IMIDs, with a median of 4 cycles for the maintenance cohort and 2 cycles for the no-maintenance cohort. For conditioning prior to salvage ASCT, 4 patients received Velcade-BEAM conditioning as part of a prospective trial at our site (NCT01653418); 3 from the maintenance cohort and 1 from the no-maintenance cohort. The rest received melphalan conditioning. Both cohorts had a CR rate of 52% (n = 16) post-salvage ASCT. Maintenance therapy after salvage ASCT consisted of lenalidomide (74%, n = 23), bortezomib (23%, n = 7), or pomalidomide (3%, n = 1). Three of the patients on bortezomib were originally started on lenalidomide but were switched due to intolerance. At time of data collection, the median follow-up was 49 months (range 9-105) for the maintenance cohort and 61 months (range 19-113) for the no-maintenance cohort. 45% (n = 14) of patients in the maintenance cohort and 90% (n = 28) of the no-maintenance cohort had relapsed. In the maintenance cohort, PFS following salvage ASCT was similar to what was observed following initial ASCT. The median estimated PFS post-salvage ASCT was 53 months (95% CI 42-64) compared to 46 months post initial ASCT (p = 0.144). Conversely, in the no-maintenance cohort PFS following salvage was only about 60% that of initial ASCT (21 months [95% CI 18-24]; compared to 33 months; p = 0.002). Conclusion: These results suggest that maintenance following salvage ASCT is associated with improved outcomes. Although patients who received maintenance post-initial ASCT were excluded, the benefits of maintenance post-salvage ASCT may extend to them as well. Ongoing prospective clinical trials will further clarify these benefits. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wildes:Janssen: Research Funding. Vij:Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Phase 2 Trial of LDE225 and Lenalidomide Maintenance Post Autologous Stem Cell Transplant for Multiple Myeloma

Blood ◽

10.1182/blood-2019-132035 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1905-1905

Author(s):

Francis K. Buadi ◽

Martha Q. Lacy ◽

Angela Dispenzieri ◽

Gabriela Perez ◽

Morie A. Gertz ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Maintenance Therapy ◽

Research Funding ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

High Dose ◽

Cell Transplant ◽

Grade 3

Background: Lenalidomide maintenance therapy post-autologous stem cell transplantation (ASCT) is associated with improved progression-free survival (PFS) and possibly overall survival in multiple myeloma (MM). However, almost all patients do relapse as a result of residual multiple myeloma cells that remain after the high-dose chemotherapy. In the myeloma setting it has been found that the hedgehog (Hh) pathway is essential for maintaining a subset of tumor causing stem cells. LDE 225 (Sonidegib) is a potent selective oral bioavailable antagonist of Smoothened (SMO), a component of the Hh signaling pathway. In in vitro experiments, LDE225 treatment of myeloma cell lines resulted in a modest inhibition of cell proliferation at increasing doses. When LDE225 was combined with lenalidomide, a more than additive effect was observed in terms of cell proliferation, an effect that was more pronounced in the context of myeloma cell lines growing in co-culture with marrow derived stromal cells. These findings form the basis of evaluation of LDE 225 as a strategy to enhance the activity of lenalidomide in the post-transplant maintenance setting. The minimal residual state post SCT provides the most optimal situation for evaluation of a drug that is likely to work by inhibiting the tumor cells that escaped high dose therapy. Methods: Multiple myeloma patients without evidence of progression, who were 60 - 120 days after a single autologous stem cell transplant (SCT), performed within 1 year of diagnosis were eligible for the study. Maintenance therapy was started approximately 3 months after SCT. Treatment consisted of lenalidomide 10 mg days 1-21 and LDE225 400 mg days 1-28 in 28-day cycles for a total of 18 cycles. The goal of the study was to assess toxicity of this combination, complete response rate (CR) progression free survival (PFS) at 1 and 2 year and overall survival (OS). CR and PFS were estimated using an exact binomial distribution and Kaplan Meier curves respectively. Results: A total of 28 patients were accrued from Jan 2014 to Aug 2016, 1 patient canceled prior to treatment and 1 patient was deemed ineligible resulting in 26 evaluable pts for CR and PFS. The median age of all pts (n=26) was 60 years (range 43-69) and 50% were males. Seventy-three percent of patients reported one treatment regimen prior to SCT, while 27% reported 2 or more prior regimens. The other characteristics of the patient are summarized in Table 1. Twenty seven pts received at least one cycle of treatment and are evaluable for toxicities (AE). Patients were treated for a median of 12.5 (range 1-18) cycles. While 10 pts (38.5%) completed protocol treatment (18 cycles), the remaining 16 pts went off treatment due to AEs (6, 23%), disease progression (3, 11.5%), refusal of further treatment (3, 11.5%) and other reasons (4, 15.4%). A grade 3 or higher AE at least possibly attributed to either drug was seen in 63%. Grade 3+ hematologic toxicities were noted in 30%, with 7% neutropenia and 4% thrombocytopenia. Notable grade 2+ non-hematologic toxicities with more than 5% incidence were dysgeusia 22%, alopecia 11%, and anorexia 7%. Grade 3+ non-hematologic toxicities were fatigue, myalgia and arthralgia each at 7%. The CR rate in evaluable patients was 46% (5 CRs and 7 sCRs) with a 95% CI of 27% - 66%. CR rate improved from 31% to 46%. VGPR or better improved from 42% to 85%. The 24-month PFS (time from SCT to progression or death due to any cause) was 73% (95% CI: 57.9 - 92.3%) with a median time to censoring of 38 months. Conclusion: Lenalidomide in combination with LDE225 as posttransplant maintenance therapy was associated with some toxicity but manageable. The combination improved the depth of response after autologous stem cell transplant. Long-term follow-up is needed to determine overall survival. Disclosures Lacy: Celgene: Research Funding. Dispenzieri:Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Alnylam: Research Funding. Gertz:Ionis: Honoraria; Alnylam: Honoraria; Prothena: Honoraria; Celgene: Honoraria; Spectrum: Honoraria, Research Funding; Janssen: Honoraria. Kapoor:Glaxo Smith Kline: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Sanofi: Consultancy, Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Russell:Imanis: Equity Ownership. Kumar:Janssen: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Sonidegib (LDE 225) is a selective oral bioavailable antagonist of Smoothened (SMO), a component of the hedgehog signaling pathway.

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