Racial and Socioeconomic Disparities in the Utilization of Autologous Stem Cell Transplant for Treatment of Multiple Myeloma in the Era of Novel Agents

INTRODUCTION: The prognosis of multiple myeloma (MM) has improved drastically in the last 20 years with the advent of novel agents, specifically with the introduction of bortezomib in late 2003. Novel agents in combination with autologous stem cell transplant (ASCT), have led to the achievement of high response rates in many patients. ASCT is now considered standard of care for all eligible patients, and previous studies have found increasing rates of ASCT in all age groups since the introduction of novel agents. Studies have also revealed disparities with decreased ASCT utilization in racial and socioeconomic minorities. This study utilizes the National Cancer Database (NCDB) to determine how the use of ASCT has changed for MM in the bortezomib era. METHODS:The NCDB was used to identify 157,443 patients diagnosed between 2004-2016 with Multiple Myeloma. Only patients with information on ASCT were included, and demographic characteristics between those patients that received and did not receive ASCT were compared. Race, insurance type, facility type, average income, education, and Charleson-Deyo comorbidity score, among other factors, were included in this analysis (Table 1). To determine the trends in ASCT over the era of novel agents, the proportion of patients receiving ASCT within these groups was trended over each year, and linear models to determine the rate of change in each group was compared. Bivariate and Multivariate regression analysis for each characteristic was used to determines odds ratios (OR) for receiving ASCT by demographic factors. RESULTS: Between 2004 to 2016 the proportion of all patients receiving ASCT as part of initial therapy more than doubled from 10.1% to 22.0%; increasing by approximately 1.06% per year on a linear regression model (R20.98) (Table 2). The greatest proportional increases were seen in Blacks, Hispanics, patients over 65 years of age, patients with higher comorbidity scores, Medicare, and patients treated at community centers. On multivariate analysis the patients that were most likely to receive ASCT (p<0.05) had private insurance (OR 5.4), were treated at academic centers (OR 7.3) and were highly educated (OR 1.7) (Table 3). For each increased year of diagnosis patients were significantly more likely (OR 1.1) to receive ASCT. Patients with a decreased chance of receiving transplant (p<0.05) were black (OR 0.6) or other non-white race (OR 0.7), Hispanic (OR 0.8), or had increased comorbidities (OR 0.4 for Charleson-Deyo score of 3 or greater). For every year of increased age, the likelihood of ASCT decreased (OR 0.92) (Table 3). DISCUSSION: In the era of novel agents, the rate of ASCT has rapidly increased each year, with the greatest increases seen in elderly patients, those with higher comorbidity indexes, and in patients who are racially and socioeconomically disadvantaged. However, significant racial and socioeconomic disparities still exist in the treatment of MM, and must be considered as treatment continues to advance. Disclosures No relevant conflicts of interest to declare.

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Improved Outcome of African American Multiple Myeloma Patients with Novel Agents and Autologous Stem Cell Transplant

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2011.12.238 ◽

2012 ◽

Vol 18 (2) ◽

pp. S296-S297

Author(s):

S. Saraf ◽

P. Patel ◽

H. Ozer ◽

D. Peace ◽

J. Quigley ◽

...

Keyword(s):

Multiple Myeloma ◽

African American ◽

Stem Cell ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Novel Agents ◽

Cell Transplant ◽

Improved Outcome

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Pericardial relapse of multiple myeloma

BMJ Case Reports ◽

10.1136/bcr-2019-233340 ◽

2020 ◽

Vol 13 (4) ◽

pp. e233340

Author(s):

Lee S Jamison ◽

Clifton Craig Mo ◽

Mary Kwok

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Poor Prognosis ◽

Stem Cell Transplant ◽

Complete Response ◽

Initial Therapy ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Extramedullary Relapse ◽

To Receive

In patients who experience relapse of multiple myeloma, upwards of 30% can have extramedullary disease. The presence of extramedullary multiple myeloma is typically associated with adverse cytogenetics and a poor prognosis. Organs most commonly involved include the liver, skin, central nervous system, pleural effusions, kidney, lymph nodes, and pancreas. We present the case of a 53-year-old man with IgA kappa multiple myeloma with the adverse cytogenetic findings of t(4;14) and 1q21 gain who had achieved a stringent complete (sCR) response after initial therapy with carfilzomib, lenalidomide and dexamethasone. Stringent complete response is defined as the normalization of the free light chain ratio in the serum and an absence of clonal cells in the bone marrow in additiion to criteria needed to achieve complete response. Prior to undergoing a planned autologous stem cell transplant, this patient experienced cardiac tamponade secondary to extramedullary relapse of his multiple myeloma which was limited to the pericardium. In response, his treatment regimen was transitioned to pomalidomide, bortezomib, dexamethasone and cyclophosphamide for three cycles after which he again achieved sCR and ultimately underwent autologous stem cell transplant. Post-transplant consolidation therapy was administered in the form of pomalidomide, bortezomib and dexamethasone, followed by pomalidomide and bortezomib maintenance, which he has continued to receive for 3 years without evidence of disease progression.

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Therapy Related MDS/AML In Multiple Myeloma Patients In The Era Of Novel Agents

Blood ◽

10.1182/blood.v122.21.3117.3117 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3117-3117

Author(s):

Morie A Gertz ◽

Suzanne R Hayman ◽

David Dingli ◽

Angela Dispenzieri ◽

Prashant Kapoor ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

The United States ◽

Lymphocytic Leukemia ◽

Novel Agents ◽

Cell Transplant ◽

Trisomy 8 ◽

To Receive

Introduction With the introduction of novel agents, survival in multiple myeloma has successively increased in the past decade. This improved survival increases the risk for late complications. Patients continue to receive melphalan therapy as a standard induction for those over the age of 65. Lenalidomide is considered a standard component of induction therapy in the United States for patients who are transplant candidates. Stem cell transplantation remains the standard of care for patients eligible to receive it. As a consequence of exposure to lenalidomide, stem cell transplant, and melphalan, the risk of late myelodysplasia and acute leukemia remains significant. We reviewed the Mayo Clinic experience with therapy-induced myelodysplasia beginning with the advent of novel agents. Patients and Methods All patients that carry the diagnosis of multiple myeloma between January 1, 2000, and September 1, 2011, were included. Patients with a synchronous diagnosis of a myeloproliferative or a myelodysplastic disorder or those who developed the myelodysplastic disorder within 15 months of first chemotherapy exposure were excluded. The date of diagnosis for the purpose of this abstract was based on first exposure to chemotherapy and not first detection of a monoclonal protein or smoldering multiple myeloma. All patients had to have morphologic verification in the bone marrow of dysplastic change consistent with therapy-related myelodysplasia. Results Of 3111 patients who had a myeloma diagnosis and first treatment after January 1, 2000, through September 1, 2011, 22 patients were identified to fulfill the criteria of myelodysplasia. There were 13 men and 9 women with a median age of 67 (46 to 82). At the time of this report, 17 have died. Prior to the development of myelodysplasia, exposure to an alkylating agent, lenalidomide, or an auto stem cell transplant was seen in 13, 15, and 10, respectively. Only one patient had been exposed to lenalidomide alone. Eighteen patients were classified as myelodysplasia. Four had acute non-lymphocytic leukemia. Metaphase cytogenetics was available in 19 and only one was normal. Twelve were hypodiploid. Trisomy 8 or abnormalities of chromosome 5 and 7 were present in 13. Seven patients received a hypomethylating agent with no clear evidence of response in any. Four patients had an allotransplant to manage the MDS/AML and only one survives 487 days after a matched-related donor allogeneic transplant. The median time from initial therapy of multiple myeloma to recognition of MDS or AML was 50.9 months (range: 15.2-146.5 months) fig 1. The median overall survival of the 22 patients is 6.5 months. Fig 2 Six of the 22 had active myeloma at the diagnosis of MDS/AML. Conclusion Myelodysplasia during the era of novel agents is a devastating complication of therapy with a very short survival and low response rate. As a time-dependent complication, the overall risk cannot be accurately estimated but has occurred in <1% of our patient population to date. Hypomethylating agents were ineffective in the seven that received it. One of four allotransplant patients remains alive. Ongoing surveillance for MDS/AML in this population is warranted and more effective therapies are needed. Disclosures: Kumar: Onyx: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

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Induction Therapy with Novel Agents and Autologous Stem Cell Transplant Overcomes the Adverse Impact of Renal Impairment in Multiple Myeloma

Clinical Hematology International ◽

10.2991/chi.d.190805.003 ◽

2019 ◽

Author(s):

Lalit Kumar ◽

Santosh Kumar Chellapuram ◽

Ramavat Dev ◽

Ankur Varshneya ◽

Satyajit Pawar ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Renal Impairment ◽

Induction Therapy ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Adverse Impact ◽

Novel Agents ◽

Cell Transplant

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Salvage Tandem Autologous Stem Cell Transplant with Consolidation for Relapsed Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.5497.5497 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5497-5497

Author(s):

Kamal Kant Singh Abbi ◽

Sonya Behrends ◽

Margarida Silverman ◽

Umar Farooq ◽

Kalyan Nadiminti ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Progressive Disease ◽

Stem Cell Transplant ◽

Progression Free Survival ◽

Autologous Stem Cell Transplant ◽

Novel Agents ◽

Cell Transplant ◽

Free Survival

Abstract Background: Therapeutic options for patients with Multiple myeloma (MM) whose disease has relapsed after a prior autologous stem cell transplant (SCT) include an expanding armamentarium of novel agents, often combined with traditional chemotherapy, or a second SCT, with no clear standard of care. Upfront tandem transplantation has been shown to improve both progression free survival and overall survival. But currently, there is little data regarding the application of tandem SCT in relapsed multiple myeloma patients. Methods: We retrospectively analyzed the outcomes of patients who underwent salvage melphalan-based tandem SCT for relapsed MM at University of Iowa Hospitals and clinics. Progression free survival (PFS) was defined as the time from date of the first salvage SCT to disease progression or death, whereas overall survival (OS) was defined from the date of the first salvage SCT to the date of death from any cause. Results: Between 2012 and 2015, 12 patients with MM received tandem autograft (total 24 transplants) for relapsed disease at our center. Conditioning was with VDT-melphalan 200mg/m2 (21/24), VDT-MEL 140mg/m2 (2/24) and Velcade, gemcitabine, BCNU, melphalan and dexamethasone (1/24). The median age at the salvage SCT was 48 years (range 37-58); 7 patients were female. 17% had high risk cytogenetics (including t(4;14), +1q, p53 loss) at the time of salvage SCT. Median time between previous transplant and progression of disease was 34 months (range 8-108). Of the 7 patients, who received re-induction therapy, 71% had chemotherapy refractory disease prior to salvage SCT. Response was assessed at 2-3 months post-SCT. Overall response rate was 92%. 7/12 (58%) patients achieved stringent complete remission, one patient achieved CR, one patient achieved near CR, 2/12 patients achieved VGPR and 1/12 had stable disease (SD). Following salvage tandem SCT, all patients received consolidation therapy with three drug combination, intended to be given for two years. Three patients have shown progressive disease at the time of analysis. The median PFS was 390 days (range 265- 1085) (Table-1); the median OS was 517 days (range 338-1085) (Table-2). Rate of progression free survival in the 10 evaluable patients at one year was 80%. There was no transplant related mortality. One patient died of progressive disease. Conclusions: Salvage tandem SCT is an effective strategy for relapsed MM and is especially effective in patients who had received less intensive therapy initially (single transplant and no maintenance therapy). Incorporation of novel agents (monoclonal antibodies and high doses of carfilzomib) into maintenance strategies may further improve outcomes. Figure 1. Progression free survival for all the patients Figure 1. Progression free survival for all the patients Figure 2. Overall survival for all the patients Figure 2. Overall survival for all the patients Disclosures Farooq: Kite Pharma: Research Funding.

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