Determinants of Receipt of Stem Cell Transplant in Elderly Medicare Beneficiaries with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5927-5927
Author(s):  
Jean Yared ◽  
Daisuke Goto ◽  
Eberechukwu Onukwugha ◽  
Rahul Khairnar ◽  
Brian Seal ◽  
...  

Abstract Introduction: Multiple myeloma (MM) is a disease of the elderly with a median age at diagnosis of 70 years. Autologous stem cell transplantation (ASCT) is a preferred treatment for younger patients but is also an option for older adults (i.e., patients >65 years) with good performance status. A previous SEER-Medicare study of MM patients diagnosed from 2000-2007 found that 5.8% underwent ASCT (Winn, et al. JNCI, 2015). The availability of ASCTs for older adults with MM has increased in the past decade due to improvement in supportive care and Medicare coverage approval. Apart from age and medical eligibility, several patient and contextual factors, such as comorbidity, may influence the receipt of ASCT in the MM population. There is limited information on the determinants of receipt of ASCT in older adults over the past decade in the US. Objective: To identify ASCT recipients among a cohort of elderly individuals with MM in order to determine characteristics associated with receiving ASCT. Specifically, this study identifies patient and contextual factors associated with the receipt of ASCT. Methods: This retrospective cohort study used Surveillance, Epidemiology, and End Results (SEER) registry and linked Medicare claims (SEER-Medicare) data. We identified individuals aged 66 and above, with an incident diagnosis of MM between 2007 and 2011 as well as claims data from 2006 to 2012. We required continuous enrollment in Medicare Parts A and B 12 months prior to and including the month of diagnosis and six months post-diagnosis. We required continuous Part D enrollment two months pre- and six months post-diagnosis. Patients were followed until death or censoring due to non-continuous Parts A and B enrollment after six months. ICD-9 and HCPCS codes were used to identify ASCT. Charlson Comorbidity Index (CCI) was used to measure the number of comorbid conditions at the time of MM diagnosis using claims one year prior to diagnosis. Student's t-test and Chi-square test of proportions were used to compare those who received ASCT to those who did not based on patient-level factors (i.e., age, gender, race, comorbidity status), geographic regions (i.e., Northeast, Midwest, West and South), and over time (diagnosed in 2007-2009 vs. diagnosed in 2010 to 2011). We also measured the time to ASCT for those who underwent ASCT. Results: Among 3,318 individuals with MM who met our inclusion criteria, 226 (6.8%) underwent ASCT during the follow-up period. ASCT recipients were younger, more likely to be male, white non-Hispanic, and have fewer comorbid conditions (Table 1). The median time from MM diagnosis to ASCT was 278 days. The rate of ASCT among recipients aged 66-69 was 23.2%, 7.3% among recipients aged 70-74, and 0.84% among those aged 75+ (p<0.001). The rate of ASCT was higher among males (8.5%) than females (5.2%) (p<0.001). Rates of ASCT were higher among those who were non-Hispanic white (8.1%), compared to those who were non-Hispanic black (3.5%) or of another race/ethnicity (4.1%) (p<0.001). Among those with CCI=0, 9.9% underwent ASCT, while 7.2% of those with CCI=1 underwent ASCT and 2.7% of those with CCI>1 underwent ASCT (p<0.001). Rates of ASCT were similar across the geographic regions (p=0.15). Of those who were diagnosed in 2007-2009, 6.0% received transplant, while 7.8% of those who were diagnosed in 2010-2011 received transplant (p=0.04). Conclusion: ASCT is performed in less than 1 in 10 patients aged 66 and older. A greater proportion of ASCT recipients were non-Hispanic white, male, diagnosed at a younger age, and had a lower comorbidity burden compared to non-transplant patients. Comparing the pre-2007 estimate from the aforementioned study to our early (2007-09) and late (2010-11) period estimates, our results illustrate an upward trend in ASCT over the past decade. We were unable to identify smoldering MM patients who would not be candidates for ASCT. This may bias our estimates downward. The aforementioned previous study found that 62% of recipients were 66-69, 32% of recipients were 70-74, while 6% were 75+ (Winn, et al. JNCI, 2015). These rates did not differ greatly from our findings indicating that the age distribution of ASCT recipients has remained stable over a 10 year period of observation. Future studies should investigate the implications of these differences for post-transplant outcomes among older MM patients. Disclosures Goto: Novartis AG: Research Funding. Onukwugha:Takeda: Research Funding; IMPAQ International: Honoraria; Bayer Healthcare: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Romanus:Takeda: Employment. Yong:Takeda: Employment. Slejko:Takeda: Research Funding; PhRMA: Research Funding; National Pharmaceutical Council: Research Funding.

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5701-5701
Author(s):  
Justin King ◽  
Mark A. Fiala ◽  
Scott R. Goldsmith ◽  
Keith E. Stockerl-Goldstein ◽  
Mark A. Schroeder ◽  
...  

Historically, high-dose therapy in combination with autologous stem cell transplants (ASCT) for multiple myeloma (MM) was reserved for younger patients. In more recent years, the use of ASCT has expanded in the older population. However, there is still limited data on the utilization and efficacy of ASCT in older patients, particularly those over the age of 75. To further evaluate this issue, we retrospectively analyzed all patients with newly diagnosed MM between the ages of 75-78, the institutional cutoff for ASCT eligibility, that were referred to the stem cell transplant unit at our institution for consultation from the years 2012-2018. Baseline characteristics, anti-myeloma treatments, and patient outcomes were abstracted through chart review. Seventy-five patients were referred to our institution. 71% were male, 29% female. 39% patients were considered ineligible for ASCT by the consulting transplant physician. Most patients were considered transplant ineligible due to comorbidities or poor performance status. Of the 46 patients eligible for ASCT, 52% underwent the procedure during their first-line therapy. The majority of those patients received reduced intensity melphalan (140 mg/m2) while 2 patients received conventional dosing (200 mg/m2). The other 22 patients eligible for ASCT declined or elected to defer the procedure and to be treated with conventional therapy. The characteristics of these three groups were similar and are detailed in Table 1. After a median follow-up of 30 months, 25% of the patients had expired. Estimated median overall survival (OS) was 71.3 months (unable to quantitate 95% CI) for all patients. Compared to transplant eligible patients, regardless of transplant receipt, those who were transplant ineligible had a 186% increase risk for death (HR 2.86; 95% CI 1.12-7.35; p = 0.029). There was also a notable trend for longer OS in those who underwent ASCT compared to those who were eligible but declined the procedure, but it was not statistically significant (HR 0.36; 95% CI 0.10-1.28; p = 0.114). At a transplant center, two-thirds of patients referred for newly diagnosed MM between the ages 75-78 were considered eligible for ASCT and one-third underwent the procedure. Outcomes were better for patients eligible for ASCT, regardless of whether they underwent the procedure. There was also a trend for better OS in patients who underwent the procedure compared to those who declined. While small sample sizes and the retrospective nature of the study limit our ability to draw conclusions, it appears that ASCT has an OS benefit among patients age 75-78. Disclosures Fiala: Incyte: Research Funding. Stockerl-Goldstein:AbbVie: Equity Ownership; Abbott: Equity Ownership. Vij:Genentech: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Wildes:Janssen: Research Funding; Carevive: Consultancy.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4580-4580
Author(s):  
Christopher P. Venner ◽  
Heather Sutherland ◽  
John Shepherd ◽  
Yasser Abou Mourad ◽  
Michael J. Barnett ◽  
...  

Abstract Abstract 4580 Background: The use of allogeneic hematopoietic stem cell transplant (alloHSCT) in the treatment of Multiple Myeloma (MM) remains controversial. Although there is hope that alloHSCT may result in a cure, relapse continues to be a significant problem. The morbidity associated with late complications of allogeneic transplantation further compounds the issues faced when addressing relapsed disease. The use of Novel Agents (NA) in this patient population has been poorly characterized. Here we present our experience of NA use in patients initially treated with alloHSCT. Patients: 108 patients underwent an allografting procedure for their MM at our center between 1989 and 2009. 84 received a fully myeloablative procedure (15 received donor lymphocyte infusion). 24 received an autologous HSCT followed by a reduced intensity allogeneic procedure. 56 have relapsed with this population making up our primary cohort for analysis. 22 patients received NAs and very few patients received them prior to transplant (4/108). Endpoints examined were post relapse survival after the initial HSCT procedure (PRS), overall survival from time of initial treatment (OS) and progression free survival (PFS) measured in months (m). Results: Of the entire cohort of 108 patients median OS was 78.6m (95% CI; 24.5–132.6). Median PFS was 23.6m (95% CI; 15.4–31.8). Of the non-relapsed patients (n = 52) the median OS was 125.9m. In this cohort 67% of the deaths occurred within 1.5 years. Of the relapsed patients (n = 56) median PFS was 18.7m (95% CI; 14.6–22.8), median PRS was 31.5m (95% CI; 17.0–46.0), and median OS was 67.0m (95% CI; 31.6–102.5). The effect of NA was examined in the cohort of relapsed patients. No significant difference was noted in PFS between those exposed to NA and those who were not exposed (19.0m (95% CI; 10.1–22.8) vs 13.7m (95% CI; 5.8–21.6); p = 0.27). Exposure to NA showed improvements in PRS (42.3m (95% CI; 7.3–77.2) vs 10.4m (95% CI; 5.2–15.7); p = 0.01, Figure 1). A trend toward superior OS was noted (71.4m (95% CI; 37.9–105.5) vs 24.6m (95% CI; 3.0–46.1); p = 0.11) although this did not reach statistical significance. Conclusion: Ongoing management of relapsed patients with multiple myeloma in the post alloHSCT setting remains a significant challenge. This retrospective study demonstrates that the use of NA is both safe and effective in treating relapsed disease. The predominant impact of these drugs is seen in the relapsed setting. Exposure to NA correlates with a 22m improvement in PRS. A 46m improvement in OS is noted however, likely due to the small cohort, it failed to reach statistical significance. Disclosures: Sutherland: Celgene: Honoraria; Orthobiotech: Honoraria. Shepherd:Celgene: Honoraria; Orthobiotech: Honoraria. Nevill:Celgene: Honoraria. Toze:Hoffman La Roche: Consultancy, Honoraria, Research Funding; Genzyme: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e20525-e20525 ◽  
Author(s):  
Tanya Marya Wildes ◽  
Sascha Alexander Tuchman ◽  
Brittany Depp ◽  
Ling Chen ◽  
Keith Stockerl-Goldstein ◽  
...  

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4736-4736
Author(s):  
Alfredo De La Torre ◽  
Andrew Gao ◽  
Timo Krings ◽  
Donna E. Reece

Abstract Introduction Progressive multifocal leukoencephalopathy (PML), caused by the John Cunningham (JC) virus, is an infection that requires immunosuppression for its manifestations and is fatal disease in many cases. (1) After asymptomatic primary infection, which occurs in childhood, the virus remains quiescent. (1,4) The classical clinical presentation is that of a subacute symptomatology that develops over weeks or months and consists of diverse sensorimotor abnormalities depending on the site of brain involvement. Approximately 22 cases of PML amongst patients with multiple myeloma (MM) have been reported in the literature between 1965 and April 2020. (5) Methods We performed a retrospective chart review of all myeloma patients who were treated at the Princess Margaret Cancer Center from 2010-2020 to identify cases of PML. Patient and disease characteristics, responses, and survival outcomes were collected from Myeloma and Stem Cell Transplant databases and electronic patient records under REB approval. Results We identified 3 cases of PML in MM patients at our center over the past 10 years, all of which occurred in patients receiving therapy containing an immunomodulatory derivative (IMID), i.e., thalidomide, lenalidomide or pomalidomide. Patient 1 A 52-year-old male with kappa light chain MM presented in 2009 on hemodialysis and received upfront bortezomib and dexamethasone followed by melphalan 200mg/m 2 and autologous stem cell transplantation (ASCT) in March 2010; maintenance with thalidomide was given until July 2011 when he presented to the ER with left-sided weakness, facial droop, and decreased strength. CT scan showed right-sided hypodensity in keeping with demyelination. PML was confirmed by MRI, lumbar puncture with positive PCR for JC virus, and a brain biopsy (Fig 1 A-C). He was treated with mirtazapine, and also developed status epilepticus controlled with phenytoin and phenobarbital. His myeloma treatment was never resumed after the diagnosis of PML due to concerns about viral reactivation. Approximately 3 years after PML diagnosis, his serum free kappa protein levels started to increase; he remained on hemodialysis but experienced no new myeloma-related organ damage and no myeloma treatment was offered. His last follow-up in clinic was in March 2019. However, he succumbed to S. pneumonia septicemia in July 2019. Case 2 A 68-year-old female with IgG kappa MM diagnosed in 2004 was treated with high-dose dexamethasone induction followed by melphalan 200mg/m 2 and ASCT and relapsed 2 years later. She commenced cyclophosphamide and prednisone until July 2011 when treatment was changed to lenalidomide and prednisone; subsequent progression in February 2014 was treated with pomalidomide/bortezomib/prednisone. In November 2014, we noticed worsening vision. Brain MRI showed hyperintensity in T2 in the occipital lobe. Her myeloma treatment was stopped and she received corticosteroids with no improvement. LP in January 2015 was positive for JC virus and the diagnosis of PML was made. She was managed with supportive measures. Her last clinic follow-up was in 2015 and the patient died from progression in September 2015. Case 3 A 52-year-old male with IgA lambda MM diagnosed in 2015 was treated with CYBOR-D induction followed by melphalan 200mg/m 2 and ASCT. He initially received lenalidomide maintenance which was changed to bortezomib due to toxicity. On progression in January of 2019 he was placed on a clinical trial of the anti-BCMA antibody drug conjugate belantamab mafodotin in combination with pomalidomide and dexamethasone on which he achieved a VGPR. In October 2020, he developed confusion and memory problems, as well as involuntary twitching. A brain MRI showed possible demyelination Two LPs were negative for JC virus, but a targeted brain biopsy confirmed the diagnosis of PML (Fig 1 D-F). His myeloma treatment was discontinued, and he was started on mirtazapine. At his most recent clinic visit in May 2021 his speech, memory and functional status had improved considerably and there were no signs of myeloma progression. Conclusion Our current series of PML in MM showcases the potential contribution of IMIDs and other novel agents--such as the newer monoclonal antibodies like belantamab mafotidin-- to the reactivation of JC virus and subsequent PML. Our series also demonstrates that neurologic improvement and longer survival can be observed with earlier management. Figure 1 Figure 1. Disclosures Reece: BMS: Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Millennium: Research Funding; GSK: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4739-4739 ◽  
Author(s):  
William I. Bensinger ◽  
Robert Vescio ◽  
Cristina Gasparetto ◽  
Elber S. Camacho ◽  
Rajneesh Nath ◽  
...  

Abstract Background: Carfilzomib is an epoxy ketone, second generation proteasome inhibitor approved for the treatment of relapsed and refractory multiple myeloma. It has shown very high activity when combined with lenalidomide and dexamethasone for the treatment of newly diagnosed patients with multiple myeloma. This is the first reported trial of carfilzomib, cyclophosphamide, and dexamethasone (CCyD) in newly-diagnosed, transplant eligible patients. Methods: This study was a multi-center Phase Ib, open-label, dose-finding study in newly diagnosed transplant eligible multiple myeloma patients (pts) studying the combination of CCyD as induction therapy prior to autologous stem cell transplant (ASCT). Pts could receive a minimum of 4 cycles and up to 6 cycles prior to ASCT. Pts were enrolled into a dose-escalation treatment cohort. A standard 3+3 dose escalation schedule was used with cohorts of carfilzomib 36 (initial), 45 and 56 mg/m2 (administered over 30 minutes on days 1, 2, 8, 9, 15 and 16) combined with 300 mg/m2 of oral cyclophosphamide weekly on days 1, 8, 15 and 40 mg of oral dexamethasone once weekly. Adverse events (AEs) were graded by NCI-CTCAE v4. Response was assessed by the IMWG criteria. Prior therapy was limited to up to 160 mg of dexamethasone or limited field radiation. Results: 28 patients were enrolled from 5 centers. Of 28 patients enrolled, 3 did not complete 4 cycles of therapy (1 proceeded to ASCT after Cycle 3) and are not evaluable for response (pts came off secondary to AE of pulmonary HTN unrelated, secondary to SAE of CHF possibly related, due to PI discretion related to maximum benefit achieved), 8 patients did not undergo ASCT (1 had PD after Cycle 5), 8 patients proceeded to ASCT (1 the aforementioned patient after Cycle 3), 6 patients have completed induction and are still pre-transplant and 4 patients are still on treatment. The median age was 64 years (range 44–74), 57% were male. Cytogenetic abnormalities included 13 patients with del(13), 4 with del(17p), 2 with t(14;16) and 1 with hypodiploidy for a total of 16 patients with high-risk cytogenetics. In the dose-escalation portion of the study, the maximum administered dose tested was 56 mg/m2 carfilzomib. There was one DLT in cycle 1, of Grade 3 dyspnea, at the 56 mg/m2 level. Drug-related AEs occurring in >20% of patients included fatigue (23%) and thrombocytopenia (31%). Thirty-one percent experienced at least one Grade ≥3 AE with dyspnea and nausea as the most common. There were no deaths on study with a median follow-up of 4.9m (range: 1.1 to 13.1m). One pt came off study after Cycle 5 for PD as evidenced by new plasmacytomas. Six patients received 36-45 mg/m2 carfilzomib on the dose escalation portion of this study and 22 patients received the maximum administered dose of carfilzomib at 56 mg/m2. One patient yet to be enrolled to obtain 20 efficacy evaluable pts at the maximum dose. Twenty-three patients were response evaluable. Median of 5.7 cycles of therapy with 2 CR, 9 VGPR, 10 PR, 1 MR and 1 PD for ≥ PR rate of 91%. Of the 12 response-evaluable patients with high risk cytogenetics, 92% were ≥ PR; of the 11 standard risk patients, 91% were ≥ PR. Of 9 patients who underwent stem cell mobilization, all collected adequate stem cells and median number of stem cells collected was 12.58 (5.07-25.31) x106 CD34+ cells/kg. Conclusions: The combination of CCyD given to untreated, symptomatic patients with myeloma was well tolerated and highly active with an 87% RR and a 48% ≥ VGPR after 4 to 6 cycles. This study compares favorably with other regimens used for induction prior to transplant for the management of newly diagnosed multiple myeloma. Disclosures Bensinger: Onyx Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Carfilzomib for use in front-line tx of multiple myeloma . Vescio:Onyx Pharmaceuticals: Honoraria, Speakers Bureau. Gasparetto:Onyx Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nath:Celgene: Consultancy. Shah:Novartis: Consultancy, Research Funding; Millennium Pharmaceuticals: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding; Array: Consultancy, Research Funding. Durie:Onyx Pharmaceuticals: IRC Other; Millennium Pharmaceuticals: IRC, IRC Other.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 54-54 ◽  
Author(s):  
Shaji Kumar ◽  
Smriti Shrestha ◽  
Mei-Jie Zhang ◽  
Angela Dispenzieri ◽  
Gustavo A. Milone ◽  
...  

Abstract Abstract 54 Despite its curative potential, the role of allogeneic stem cell transplant (allo-SCT) in MM has been limited by high treatment related mortality (TRM). Autologous stem cell transplant (auto-SCT) thus remains the standard of care for eligible patients (pts) with MM. Recently interest in allo-SCT has been increasing due to the incurable nature of MM, better risk stratification models, improved supportive care and finally the increasing experience with less toxic reduced intensity conditioning. We analyzed the trends in practice of allo-SCT for MM over the past two decades. A total of 1211 pts undergoing allo-SCT for MM between 1989 and 2005, reported to the CIBMTR were analyzed in three cohorts based on year of allo-SCT: 1989–1994 (n=346), 1995–2000 (n=285), and 2001–2005 (n=580). Probabilities of progression-free survival (PFS) and overall survival (OS) and cumulative incidence estimates of TRM and relapse were calculated. Patient characteristics are summarized in table 1. Patients transplanted in the later cohort (2001–2005) were of higher age with 53% above age 50 years (vs. 12% in 1989–1994). There was decreasing use of myeloablative regimens and bone marrow grafts over time (82% vs. 62% vs. 9% for myeloablative regimens and 99%, 62% and 13% for marrow grafts respectively). Increasing number of pts in the later cohort received an auto-SCT prior to allo-SCT (Table 1). The proportion of unrelated allo-SCTs increased over time (5% vs. 21% vs. 33%). Graft versus host (GVH) prophylaxis changed over time with increasing use of cyclosporine with agents other than methotrexate and increasing use of ATG in the recent years. Median survival increased over the three time periods from 1989 – 2005: 11.1 months (mos.) vs. 12.2 mos vs. 20.3 mos. The 100 day mortality decreased steadily over successive time periods; 35% (95% CI; 29–31), 29% (24–35) and 19% (16–23) respectively. Similarly, the TRM at 5 years remained steady between the first two periods, but decreased in the last period (40 & 48% vs. 29%). The incidence of chronic GVHD increased in the later cohort but the incidence of acute GVHD was similar over the years. While PFS was the lowest for the most recent group (15% at 5 years), the overall survival at 5 years was similar among the groups (30, 32, and 29 mos). Long term PFS at 10 years was 18% in the 1989–1994 cohort and 17% in 1995–2000. Long term OS at 10 years was 23% in 1989 – 1994 and 1995–2000 cohorts. Results are summarized in table 1. A clear trend towards reduced intensity conditioning, unrelated donor SCT, use of PBSC grafts and selection of older patients was noted. There was increasing use of tandem auto-allo SCT with an increasing proportion of patients with a prior auto-SCT. While the TRM has decreased significantly in the last cohort, this did not translate into an improvement in survival primarily because of increased risk of relapse in the latter cohort. Long term (>10yr) progression free survival which may approach a cure has remained unchanged over the past two decades at <20%. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3469-3469
Author(s):  
Morie Abraham Gertz ◽  
Dennis Gastineau ◽  
Martha Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
...  

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.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4060-4060
Author(s):  
Rachid Baz ◽  
Melissa Alsina ◽  
Kenneth H. Shain ◽  
Jennifer Paleveda ◽  
Nancy Hillgruber ◽  
...  

Abstract Abstract 4060 Introduction: Rajkumar et al. reported improved survival with lenalidomide and low dose dexamethasome as compared with lenalidomide and high dose dexamethasone (Rajkumar V, Lancet Oncol 2010). In addition, we reported promising outcomes of a retrospective cohort of newly diagnosed multiple myeloma patients treated with single agent lenalidomide(Baz R Leuk Lymphoma. 2010). Accordingly, we conducted this prospective single center open label study to evaluate the efficacy of a response adapted approach using single agent lenalidomide in older adults with newly diagnosed standard risk multiple myeloma. Patients/Methods: Eligible patients had symptomatic multiple myeloma without high risk features (b2microglobulin (b2m) ≤5.5, absence of t(4;14), t(14;16), 17p deletion, aneuploidy or 13q by metaphase cytogenetics) and were not eligible or not willing to receive high-dose therapy and stem cell transplant. Patients received lenalidomide 25 mg PO D1–21 every 28 days for 2 cycles. If patients had a minimal response or better (MR, 25% reduction in serum M spike) after 2 cycles, they continued on single agent lenalidomide until progressive disease. If patients had stable disease after 2 cycles, prednisone 100 mg PO D1–5 was added to their lenalidomide. In the event of progressive disease on single agent lenalidomide or on lenalidomide/prednisone, therapy was changed to lenalidomide (at the tolerated dose) and dexamethasone 40 mg PO weekly. Thromboprophylaxis was with aspirin, warfarin or low molecular weight heparin. Responses were per IMWG response criteria. The study was approved by the institutional review board. Results: Between February 2010 and May 2012, 22 patients were screened and 19 were eligible. The median age was 75 years (range 65–83) and 12 were males. Per protocol, no patient had ISS stage 3 disease but 8 patients had ISS stage 2 and 11 stage 1 (median b2m was 3.2 mg/L (range 2.2–5.5)). 5 patients had 13q deletion by FISH alone, 4 had t(11;14), another 3 had trisomy 11, and 2 had trisomy or tetrasomy 1q. The median baseline creatinine clearance was 66.5 ml/min (range 43–109). After 2 cycles of single agent lenalidomide, 9 patients (47%) had a PR (partial response), 6 (32%) MR, 3 (16%) stable disease (SD), and 1 (5%) progressive disease. The best response to single agent lenalidomide was as follows: 3 had a stringent complete response sCR (16%), 1 (5%) a very good partial remission (VGPR), 8 PR (42%), 4 MR (21%), 2 SD (11%) and 1 PD (5%). The estimated 1 year PFS to single agent lenalidomide is 80%. Five patients required the addition of dexamethasone with the following responses: 1 VGPR, 1 PR, 1 MR, 1 SD and 1 PD; Three patients required the addition of prednisone and the response to lenalidomide prednisone was 1PR, 1 MR, 1 SD. Five patients went off study, 2 for PD and 3 withdrew consent (2 were in PR at the time and 1 in SD). The estimated 1 year PFS for the protocol therapy is estimated at 94%. Eleven patients had dose reduction in lenalidomide; 5 patients to 15mg and 6 patients to 10 mg. Grade 3/4 neutropenia, thrombocytopenia, anemia, febrile neutropenia and fatigue occurred in 58%, 5%, 10%, 5% and 5% of patients respectively. Conclusion: In this patient population, single agent lenalidomide results in an ORR (PR and better) of 63% and clinical benefit rate (MR and better) of 84% with only a quarter of patients requiring the addition of dexamethasone. A response adapted therapy using single agent lenalidomide is safe and effective in older adults with standard risk myeloma sparing dexamethasone toxicities from the majority of patients. Updated results for ongoing accrual of up to 30 evaluable patients will be presented at the meeting. Disclosures: Baz: Celgene, Millennium, Bristol Myers Squibb, Novartis: Research Funding. Off Label Use: lenalidomide for newly diagnosed multiple myeloma. Alsina:Millenium: Consultancy, Research Funding. Finley-Oliver:celgene: Speakers Bureau.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4265-4265 ◽  
Author(s):  
Mabel Rodriguez ◽  
Nelly G. Adel ◽  
Sean Devlin ◽  
Sergio A Giralt ◽  
Heather Landau

Abstract Abstract 4265 Background: High-dose melphalan (MEL) followed by autologous stem cell support has been an integral component of multiple myeloma (MM) therapy since the 1980's. In general, high-dose melphalan is well-tolerated however grade 3 and 4 mucositis has been reported in up to 75% of patients (Lilleby et al. Bone Marrow Transpl, 2006). The efficacy of cryotherapy in preventing mucositis was initially documented in patients receiving infusional 5- fluorouracil (Rubenstein et al. Cancer, 2004). It is presumed that vasoconstriction reduces exposure of the oral mucosa to chemotherapy. Due to similar pharmacokinetic properties of melphalan including its short half life, cryotherapy has been used in MM patients undergoing MEL and stem cell transplant (SCT) with small series and one randomized trial supporting its use (Lilleby et al. Bone Marrow Transpl, 2006). At Memorial Sloan-Kettering Cancer Center, ice chips administered for 30 minutes before, during and after melphalan administration was adopted in March 2011 for all MM patients receiving MEL (≥ 140 mg/m2). In this study we sought to determine if the incidence of mucositis has been reduced since instituting cryotherapy into our standard practice. Methods: We retrospectively identified MM patients who received MEL 140 or 200 mg/m2 prior to SCT between January 1, 2009 and June 12, 2012 using our pharmacy database and electronic medical record. We analyzed two groups of patients by date of SCT and confirmed that patients transplanted prior to 3/2011 did not receive cryotherapy while all others did. Mucositis grade was recorded as documented by medical staff or determined by the investigators using the CTCAE version 4 criteria. Disease and treatment characteristics were collected in addition to narcotic use, total parenteral nutrition (TPN) requirement, and days of hospitalization. Fisher's exact test was used to compare the proportion of patients with mucositis, severe mucositis (defined as grade 3 or higher) and those requiring patient controlled analgesia (PCA), by cryotherapy use. Logistic regression was used to adjust for prior radiation and the number of prior lines of therapy. The number of hospital days was compared using a t-test. Results: During the study period, 214 patients underwent one or more autologous SCTs for MM; for patients who had more than one, only the initial SCT was included in this analysis. Of 214 patients, 85 (40%) received cryotherapy of whom 34% developed mucositis compared to 47% who did not receive cryotherapy (P = 0.08). Grade 3 mucositis was seen in 2% and 16% of patients who did and did not receive cryotherapy respectively (P = 0.004). No patient in either group developed grade 4 mucositis. After adjusting for radiation and lines of prior therapy the association between grade 3 mucositis and cryotherapy remained significant (OR: 0.13 (0.02, 0.47); P = 0.01). PCA use was lower in patients who received cryotherapy (19%) compared to those who did not (37%) (P = 0.01), with the median duration of use being 5 days in both groups. TPN was not required for any patient. Hospital days were similar in both groups (P = 0.88). Conclusion: Cryotherapy administration at the time of high-dose melphalan reduces the incidence of severe mucositis and PCA use. Cryotherapy is readily available and should be offered to all MM patients receiving ≥ 140 mg/m2 of melphalan. Disclosures: Landau: Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Research Funding.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5397-5397 ◽  
Author(s):  
Beth Faiman ◽  
Surbhi Sidana ◽  
Paul Elson ◽  
Kellie Bruening ◽  
Hien K. Duong ◽  
...  

Abstract Background We hypothesized lenalidomide (len) related diarrhea (LRD) may correlate with activation of an immune response against multiple myeloma (MM) based on colon biopsies that showed crypt apoptosis reminiscent of GVHD in 3 MM patients with severe LRD but without prior allogeneic stem cell transplantation or gastrointestinal disorder. To investigate whether survival may be influenced by the presence of LRD we performed a retrospective chart review. Methods Patients who developed symptomatic MM on or after 1/1/2005 as defined by the start of anti-MM therapy and had been on len for at least 6 consecutive months by 12/31/2010 were included in the analysis. Significant LRD was considered present if the treating physician attributed the diarrhea to len and recommended supportive therapy in at least two clinic notes.  The first time treatment for LRD was recommended was used as the date of onset of LRD. As possible confounding factors age at the start of len therapy, number of prior regimens, prior high dose chemotherapy with autologous stem cell transplant (ASCT), and use of antineoplastic agents other than corticosteroids at any time during the continuous len therapy were collected. The primary outcome was overall survival (OS), which was calculated from the start of len. Fisher’s exact test, Mann-Whitney test, and the logrank test were used to compare characteristics and duration of len between patients with and without LRD. Proportional hazards models were used to assess the impact of LRD on OS. The lag between the start of len and development of LRD was accounted for by treating LRD as a time-varying covariate in these models. Results 161 patients were identified, 47 (29%) had LRD, and 59 (37%) died during follow up. LRD and no LRD groups were balanced for gender, age, number of prior regimens, prior transplant, and use of antineoplastic agents other than corticosteroids with len, but len treatment duration differed; LRD patients had received a median of  43.4 consecutive months of len (range 5.8-82.9) compared to 14.6 (range 5.9-89) for patients without LRD (p=0.001). Onset of LRD occurred after a median of 17.7 months (range 0.3-75.4) of len therapy. In multivariable analyses, development of LRD (HR 0.46, 95% C.I. 0.21-1.00, p=0.05) was associated with improved OS as were the number of prior therapies (0-2, vs >2, HR 0.16, 95% C.I. 0.08-0.32, p<0.0001) and no use of antineoplastic therapy other than corticosteroids during len therapy (HR 0.52, 95% C.I. 0.29-0.93, p=0.03), while age and prior ASCT (p=0.52 and 0.49, respectively) were not. Conclusion Late onset of lenalidomide related diarrhea (LRD) is compatible with an immune mediated effect that may signal anti-MM immune activity since LRD requiring supportive measures correlated with survival in MM in analyses that adjusted for lag time. While more study is needed to prove this hypothesis, our findings suggest that diarrhea on len may argue for continued therapy rather than discontinuation. Disclosures: Faiman: Celgene: Consultancy, Speakers Bureau; Millennium: Consultancy, Speakers Bureau; Onyx: Consultancy, Speakers Bureau. Duong:Celgene: Honoraria, Research Funding. Valent:Celgene: Speakers Bureau; Millennium: Speakers Bureau. Reu:Celgene: Research Funding; Onyx: Speakers Bureau.


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