scholarly journals Safety and Efficacy of Lenalidomide in Relapsed or Refractory Multiple Myeloma

2011 ◽  
Vol 6 ◽  
pp. CMO.S7275 ◽  
Author(s):  
Adrian Alegre ◽  
Isabel Vicuña ◽  
Beatriz Aguado
Keyword(s):  
Multiple Myeloma ◽  
Venous Thromboembolism ◽  
Survival Outcomes ◽  
Second Primary ◽  
Safety And Efficacy ◽  
Depth Of Response ◽  
Increased Risk ◽  
First Relapse ◽  
Immunomodulatory Drug ◽  
Second Primary Malignancies

Lenalidomide is an oral immunomodulatory drug that has helped improve outcomes in multiple myeloma (MM) patients. Combination lenalidomide and dexamethasone (Len+Dex) has been shown to increase response rates and prolong survival compared with dexamethasone alone in patients with relapsed or refractory MM (RRMM). Clinical benefit may be greatest when Len+Dex is given at first relapse, and continued treatment appears to provide greater depth of response and improved survival outcomes. The most common adverse events associated with Len+Dex are cytopenias, which are predictable and manageable. Len+Dex is associated with an increased risk of venous thromboembolism, which necessitates adequate prophylaxis. The risk of second primary malignancies does not appear to be increased in patients with RRMM treated with lenalidomide-based therapy. Here we review the safety and efficacy of Len+Dex in RRMM, and provide an overview of data from Spain on the use of Len+Dex in RRMM.

scholarly journals Persistent Overall Survival Benefit and No Increased Risk of Second Malignancies With Bortezomib-Melphalan-Prednisone Versus Melphalan-Prednisone in Patients With Previously Untreated Multiple Myeloma

2013 ◽  
Vol 31 (4) ◽  
pp. 448-455 ◽  
Author(s):  
Jesús F. San Miguel ◽  
Rudolf Schlag ◽  
Nuriet K. Khuageva ◽  
Meletios A. Dimopoulos ◽  
Ofer Shpilberg ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Final Analysis ◽  
Incidence Rates ◽  
Phase Iii ◽  
Second Primary ◽  
Risk Of Death ◽  
Increased Risk ◽  
Second Primary Malignancies

Purpose This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies. Patients and Methods In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients. Results After median follow-up of 60.1 months (range, 0 to 74 months), there was a 31% reduced risk of death with VMP versus MP (hazard ratio [HR], 0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was seen across prespecified patient subgroups (age ≥ 75 years, stage III myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP patients and 73% of MP patients had received subsequent therapy. Time to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was longer with VMP than with MP. Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR, 0.914). Following VMP/MP, incidence proportions of hematologic malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted incidence rates (0.017/0.013 per patient-year) were similar and were consistent with background rates. Conclusion VMP resulted in a significant reduction in risk of death versus MP that was maintained after 5 years' follow-up and despite substantial use of novel-agent-based salvage therapies. There is no emerging safety signal for second primary malignancies following VMP.

scholarly journals Incidence of Second Primary Malignancies and Association with Treatment in US Veterans with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1806-1806
Author(s):  
Nathanael Fillmore ◽  
Sarvari Venkata Yellapragada ◽  
Cenk Yildirim ◽  
Aimaz Afrough ◽  
Adanma Anji Ayanambakkam Attanathi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Research Funding ◽  
Treatment Initiation ◽  
Smoking Status ◽  
Agent Orange ◽  
Second Primary ◽  
Increased Risk ◽  
Second Primary Malignancies ◽  
Central Cancer Registry

Background: In the recent decade, there have been dramatic improvements in multiple myeloma (MM) survival, owing principally to developments in therapeutic options. However, these developments have also raised concerns as to increase in second primary malignancies (SPMs) attributable to these therapies. For example, a Swedish study showed an increased risk of developing acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) in MM patients (11.51 fold), along with 1.19-fold increased risk of non-hematologic malignancies. However, it is presently unclear whether this increase is related to therapy or other factors such as host, environment or behavioral patterns. Here, we study incidence of SPM and association with demographics, exposure, and therapy in a large population in the US Veterans Affairs (VA) healthcare system. Methods: We used the VA's nationwide Corporate Data Warehouse to identify patients diagnosed with MM from 1999 to 2017, as well as their age, race, therapy at induction, stem-cell transplant status, and exposure status. For each patient, we identified the first SPM after MM treatment initiation using the VA Central Cancer Registry. We excluded patients who had records of malignancies prior to MM treatment initiation. Results: We identified 14,261 patients meeting the inclusion criteria, of whom 552 (3.9%) had SPMs, consistent with prior literature. Median age at MM diagnosis was 69.22 years overall (95% CI 51.98-84.76), 66.7 years (52.03-83.86) for those with SPM, and 69.32 years (51.99-) for those without SPM. Median age at diagnosis of SPM was 70.2 years (55.43-86.75). Median time from MM treatment initiation to SPM was 2.38 years (0.09-9.37). Of the 552 observed SPMs, 69 (12.4%) were hematologic (25 MDS, 19 lymphoma, 15 acute leukemia, 6 chronic leukemia, 4 MPN) while 84.5% (466) were oncologic. Prostate cancer was the most common SPM (n=125, 22.6%). We did not observe statistically significant differences in incidence of SPM by smoking status (4.1% among current/former smokers vs 3.7% among never smokers; P=0.347), or Agent Orange exposure (4.2% among those exposed vs 3.8% among those not exposed; P=0.476). We also examined the relationship of common treatments to SPM. SPM is more common among those exposed to lenalidomide (4.3% vs 3.4%, p=0.003), bortezomib (4.8 vs 3.3%, p<0.001), and transplant (7.5% vs 3.5%, p<0.001). Considering only therapy at induction, SPMs occur among 3.3% of those receiving lenalidomide/dexamethasone (Rd), 4.0% of those receiving bortezomib/dexamethasone (Vd), and 4.5% of those receiving RVd (p=0.11). Among those who also received transplant, SPM occurs in 6.0%, 6.6%, and 8.7% of those receiving Rd, Vd, and RVd, respectively (p=0.49). And, among those who did not receive transplant, SPM occurs in 3.1%, 3.5%, and 3.7% of cases, respectively (p=0.52). Conclusion: In comparison to data from the VA Central Cancer Registry on cancer incidence at the VA in general, the incidence of SPM (3.9%) that we report among MM patients is substantially higher than the overall incidence of malignancy in the VA (0.78%). Moreover, we find that common risk factors for developing malignancy, including smoking status and exposure to Agent Orange, are not significantly associated with developing SPM after MM diagnosis. In contrast, we find that therapy utilization, particularly transplant, is associated with significant increases in susceptibility to SPM. Better understanding of these risk factors is needed to appropriately assess the tradeoff of decreased myeloma-related mortality, but potentially increased risk of secondary malignancies with common myeloma therapy options. Disclosures Yellapragada: Novartis: Employment, Other: Spouse Employment ; Celgene: Research Funding; BMS: Research Funding; Takeda: Research Funding. Munshi:Abbvie: Consultancy; Adaptive: Consultancy; Adaptive: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Takeda: Consultancy; Oncopep: Consultancy; Oncopep: Consultancy; Abbvie: Consultancy.

Continued Overall Survival Benefit After 5 Years' Follow-up with Bortezomib-Melphalan-Prednisone (VMP) Versus Melphalan-Prednisone (MP) in Patients with Previously Untreated Multiple Myeloma, and No Increased Risk of Second Primary Malignancies: Final Results of the Phase 3 VISTA Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 476-476 ◽  
Author(s):  
Jesús F San Miguel ◽  
Rudolf Schlag ◽  
Nuriet K Khuageva ◽  
Meletios Athanasios Dimopoulos ◽  
Ofer Shpilberg ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Second Primary ◽  
Phase 3 ◽  
Increased Risk ◽  
Equity Ownership ◽  
Second Primary Malignancies ◽  
Patient Subgroups

Abstract Abstract 476FN2 Background: Data from the initial report of the international, multicenter, phase 3 VISTA trial demonstrated that VMP was superior to MP across all efficacy endpoints, including response rates, time to progression, and overall survival (OS), in previously untreated multiple myeloma (MM) patients ineligible for high-dose therapy. Following this report, centralized assessment of response/progression was stopped and, per protocol, patients were followed for up to 4.5 years post-last patient in date for survival and the use of subsequent anti-MM therapy only. An updated analysis, conducted after a median follow-up of 36.7 months, demonstrated a continued significant OS benefit with VMP. Here we report the final updated OS analysis of VISTA after 5 years of follow-up, including an exploratory analysis of the risk of second primary malignancies (SPMs), an important issue for MM patients receiving long-term therapy. Methods: Patients were randomized (1:1) to receive nine 6-week cycles of VMP (N=344; bortezomib 1.3 mg/m2, days 1, 4, 8, 11, 22, 25, 29, and 32, cycles 1–4, days 1, 8, 22, and 29, cycles 5–9; melphalan 9 mg/m2 days 1–4, prednisone 60 mg/m2, days 1–4, all cycles) or MP (N=338) alone. Patients were followed at least every 12 weeks for survival and subsequent therapy use. Data on SPMs were collected during February 2011 by surveying all study sites to capture information for 655 (96%) patients. Results: After median follow-up of 60.1 months, with only 5% of patients lost to follow-up, median OS was 56.4 versus 43.1 months for patients randomized to VMP compared to MP (HR 0.695, p=0.0004), reflecting a 31% reduced risk of death with VMP (Figure); 5-year OS rates were 46.0% and 34.4%, respectively. This compares favorably with the 6.6-month increase in median OS in a meta-analysis of six phase 3 trials of MP-thalidomide vs MP (Fayers et al, Blood 2011). The OS benefit with VMP was seen across patient subgroups, including those aged ≥75 years (median 50.7 vs 32.9 months, HR 0.71), patients with ISS stage III MM (median 42.1 vs 30.5 months, HR 0.67), and those with creatinine clearance <60 mL/min (median 56.8 vs 36.7 months, HR 0.70), but no significant difference was observed in the small subgroup of patients with documented high-risk cytogenetics (n=46). At data cut-off (March 24, 2011), 63% of VMP and 73% of MP patients had received subsequent MM therapies; use of subsequent therapies was generally similar between arms, except for a higher proportion of MP patients receiving subsequent bortezomib (43% vs 22%). Time to next treatment (median 27.0 vs 19.2 months; HR 0.557, p<0.0001) and treatment-free interval (median 16.6 vs 8.3 months, HR 0.573, p<0.0001) were superior with VMP vs MP. Among all patients who had received subsequent therapies, OS was superior with VMP vs MP (median 55.7 vs 46.4 months; HR 0.745, p=0.0162). A 30-month landmark OS analysis demonstrated superior survival from landmark among all VMP patients (median not reached) and among VMP patients who had received any subsequent therapy (median 28.2 months) vs MP patients who had received subsequent bortezomib (median 23.0 months). Taking into account the longer observation period due to prolonged survival on the VMP arm, analyses of SPM risk (Table) showed no difference in incidence proportions or ‘exposure'-adjusted incidence rates between arms. Rates on both arms (VMP 0.0166, MP 0.013 per patient-year) were consistent with background incidence rate in the general population aged 65–74 years (0.019, SEER database). Conclusions: VMP resulted in a substantial long-term OS benefit vs MP (13.3-month increase in median), which was seen across patient subgroups and regardless of extensive subsequent therapy. There was no increased risk of SPMs identified with VMP vs expected background rates. Disclosures: San Miguel: Janssen-Cilag: Consultancy; Celgene: Consultancy; Millennium Pharmaceuticals, Inc: Consultancy. Dimopoulos:Millennium Pharmaceuticals, Inc.: Honoraria; Ortho Biotech: Consultancy, Honoraria. Kropff:Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Spicka:Janssen-Cilag: Honoraria; Celgene: Honoraria. Petrucci:Janssen-Cilag: Honoraria; Celgene: Honoraria. Palumbo:Janssen-Cilag: Honoraria; Celgene: Honoraria. Dmoszynska:Janssen-Cilag: Research Funding. Delforge:Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Mateos:Janssen-Cilag: Honoraria; Celgene: Honoraria. Anderson:Celgene: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Esseltine:Millennium Pharmaceuticals, Inc.: Employment; Johnson & Johnson: Equity Ownership. Liu:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Deraedt:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Cakana:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. de Velde:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Richardson:Celgene: Consultancy; Janssen Research & Development: Consultancy; Millennium Pharmaceuticals, Inc.: Consultancy.

scholarly journals Second Primary Malignancies Among Patients with Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1621-1621
Author(s):  
Hannah P. Cutshall ◽  
Kevin D. Arnold ◽  
Elizabeth E. Brown
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Hematologic Malignancy ◽  
Absolute Risk ◽  
Individual Treatment ◽  
Second Primary ◽  
Excess Absolute Risk ◽  
Increased Risk ◽  
Treatment Data ◽  
Second Primary Malignancies

Abstract Introduction. Treatment for multiple myeloma (MM) has undergone significant transformation in the past decade with the introduction of novel therapeutic agents, including proteasome inhibitors (PI), immunomodulatory imides (IMiD) and monoclonal antibodies (mAb), leading to significant improvements in drug tolerability, treatment response and overall survival. As overall survival improves, patients with MM are at increased risk of developing second primary malignancies. Therefore, we evaluated the incidence of second primary malignancies among patients with MM. Methods. Using data from 30,630 1-year survivors of MM reported to 13 cancer registries that constitute the Surveillance, Epidemiology, and End Results (SEER) program (1992-2015; median survival time, 4.5 years), we calculated standardized incidence ratios (SIR) for all second primary malignancies, any solid and any hematologic malignancy and cancer sites among patients with MM, stratified by calendar year of first primary diagnosis consistent with advances in treatment for MM (1992-1999, 2000-2007, 2008-2015). Individual treatment data were unavailable. Excess absolute risk (excess cancer risk per 10,000 person-years) was calculated as ([observed cancers minus expected cancers]/person-years) multiplied by 10,000. Hazard ratios were calculated using Cox proportional hazards adjusted for confounders. Analyses were conducted using SAS v.9.4. Results. Overall, among 30,630 1-year survivors of first primary MM, the standardized incidence of any second primary malignancy was significantly increased (n=1,962; SIR=1.15, 95% confidence interval [CI], 1.10-1.20; P&lt;0.0001) and SIRs were elevated in each of the three calendar periods (1992-1999, SIR=1.14; 2000-2007, SIR=1.11; 2008-2015, SIR=1.22). Of all the second primary malignancies, the incidence of any solid tumor was increased (n=1,584; SIR=1.05, 95% CI 0.99-1.10; P=0.09), albeit not significantly, with SIRs for specific solid tumor sites ranging from 0.80 to 2.23. In contrast, the incidence of any hematologic malignancy overall was significantly increased (n=317; SIR=2.28, 95% CI 2.03-2.54; P&lt;0.0001) with the largest SIRs observed for any leukemia (SIR=5.86, 95% CI 4.91-6.94; P=&lt;0.0001) and SIRs for leukemia subtypes ranging from 2.07 to 14.87. The SIR for any lymphoma was also increased but to a lesser extent (SIR=1.57, 95% CI 1.35-1.82; P&lt;0.0001). Notably, SIRs for any leukemia decreased over the three time periods (1992-1999, SIR=6.40; 2000-2007, SIR=5.77; 2008-2015, SIR=5.51) whereas SIRs for any lymphoma increased (1992-1999, SIR=1.21; 2000-2007, SIR=1.60; 2008-2015, SIR=1.81) leading to an excess absolute risk of any hematologic malignancy of 1.5 per 10,000 person-years in the latest calendar period. No differences were observed by sex or ancestry. Discussion. We confirm that MM patients are at increased risk of second primary malignancies, and particularly other blood cancers. The transposition of leukemia and lymphoma incidence over time may reflect the effect of treatment changes in recent years. Additional studies, which include individual treatment data and longer follow up time from large and diverse populations, are required to further define these relationships. Disclosures No relevant conflicts of interest to declare.

scholarly journals VTE Rates and Safety Analysis of Newly Diagnosed Multiple Myeloma Patients Receiving Carfilzomib-Lenalidomide-Dexamethasone (KRD) with or without Rivaroxaban Prophylaxis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1835-1835 ◽  
Author(s):  
Katrina M Piedra ◽  
Hani Hassoun ◽  
Larry W. Buie ◽  
Sean M. Devlin ◽  
Jessica Flynn ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Research Funding ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Cancer Trial ◽  
Oncology Research ◽  
Increased Risk

Introduction Immunomodulatory agents (IMiD's) are associated with an increased risk of venous thromboembolism (VTE), particularly when combined with high dose steroids. Studies evaluating the use of lenalidomide-bortezomib-dexamethasone (RVD) and carfilzomib-lenalidomide-dexamethasone (KRD) in the frontline setting for multiple myeloma (MM) have reported a 6% and 24% incidence of thrombosis, respectively, despite primary thrombotic prophylaxis with aspirin (ASA) (Richardson, et al. Blood. 2010; Korde, et al. JAMA Oncol 2015). Recent data, including the Hokusai VTE Cancer Trial, have suggested that safety and efficacy of direct oral anticoagulants (DOACs) are preserved in the setting of treatment of solid malignancy-associated thrombosis (Raskob, et al. N Engl J Med. 2018; Mantha, et al. J Thromb Thrombolysis. 2017). Despite this data, there is limited experience and use of DOACs in prevention of thromboses in the setting of hematologic malignancies, specifically MM. After careful review of literature, since early 2018, we changed our clinical practice and routinely placed newly diagnosed MM (NDMM) patients receiving KRD at Memorial Sloan Kettering Cancer Center (MSKCC) on concomitant rivaroxaban 10 mg once daily, regardless of VTE risk stratification. In the following abstract, we present VTE rates and safety data for newly diagnosed MM patients receiving RVD with ASA vs. KRD with ASA vs. KRD with rivaroxaban prophylaxis. Methods This was an IRB-approved, single-center, retrospective chart review study. All untreated patients with newly diagnosed MM, receiving at least one cycle of RVD or KRD between January 2015 and October 2018 were included. The period of observation included the time between the first day of therapy until 90 days after completion of induction therapy. Patients were identified by querying the pharmacy database for carfilzomib or bortezomib administration and outpatient medication review of thromboprophylaxis with rivaroxaban or ASA. VTE diagnoses were confirmed by ICD-10 codes and appropriate imaging studies (computed tomography and ultrasound). Descriptive statistics were performed. Results During the observation period, 241 patients were identified to have received RVD or KRD in the frontline (99 RVD with ASA; 97 KRD with ASA; 45 KRD with rivaroxaban). Baseline characteristics were well distributed among the three arms, with a median age of 60 (30-94) in the RVD ASA arm, 62 (33-77) in the KRD ASA arm, and 60 (24-79) in the KRD rivaroxaban arm. Patients had International Staging System (ISS) stage 3 disease in 13% (N=13), 9.3% (N=9), and 11% (N=5) of the RVD ASA, KRD ASA, and KRD rivaroxaban arms, respectively. Median weekly doses of dexamethasone were higher in both KRD arms, 40 mg (20-40) vs. 20 mg (10-40) in the RVD ASA arm. The average initial doses of lenalidomide were 22 mg in the RVD ASA arm compared to 25 mg in both the KRD ASA and KRD rivaroxaban arms. After querying the pharmacy database, no patients were identified to have a history or concomitant use of erythropoietin stimulating agent (ESA) use. Treatment-related VTE's occurred in 4 patients (4.0%) in the RVD ASA arm, 16 patients (16.5%) in the KRD ASA arm, and in 1 patient (2.2%) in the KRD rivaroxaban arm. Average time to VTE was 6.15 months (Range 5.42, 9.73) after treatment initiation in the RVD ASA group, while it was 2.61 months (Range 0.43, 5.06) in the KRD ASA group and 1.35 months in the KRD rivaroxaban group. Minor, grade 1 bleeding events per the Common Terminology Criteria for Adverse Events (CTCAE) were identified in 1 (1.1%) patient in the RVD ASA arm, 5 (5.2%) patients in the KRD ASA arm, and 1 (2.2%) patient in the KRD rivaroxaban arm. Conclusion More efficacious MM combination therapies have been found to increase the risk of VTE when using ASA prophylaxis, indicating better thromboprophylaxis is needed. We found patients receiving ASA prophylaxis with KRD were more likely to experience a VTE and these events occurred earlier compared to patients receiving ASA prophylaxis with RVD. Importantly, the rate of VTE was reduced to the same level as ASA prophylaxis with RVD when low-dose rivaroxaban 10 mg daily was used with KRD, and without necessarily increasing bleeding risk. Our retrospective data support the development of prospective clinical trials further investigating DOAC use in thromboprophylaxis for NDMM patients receiving carfilzomib-based treatments. Figure Disclosures Hassoun: Novartis: Consultancy; Janssen: Research Funding; Celgene: Research Funding. Lesokhin:BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Research Funding; GenMab: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Genentech: Research Funding; Juno: Consultancy, Honoraria. Mailankody:Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria. Smith:Celgene: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics and Precision Biosciences: Consultancy. Landgren:Theradex: Other: IDMC; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Karyopharm: 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; Merck: Other: IDMC; Sanofi: Membership on an entity's Board of Directors or advisory committees; Adaptive: 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, Research Funding. OffLabel Disclosure: Off-label use of rivaroxaban for outpatient prophylaxis of venous thromboembolism (VTE) will be explicitly disclosed to the audience.

scholarly journals Incidence of Second Primary Malignancies and Peripheral Sensory Neuropathy in Patients with Multiple Myeloma Receiving Daratumumab Containing Regimen

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5550-5550 ◽  
Author(s):  
Thura Win Htut ◽  
Donald P. Quick ◽  
Myint Aung Win ◽  
Sriman Swarup ◽  
Anita Sultan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Control Group ◽  
Second Primary ◽  
Peripheral Sensory Neuropathy ◽  
Antitumor Effects ◽  
Refractory Multiple Myeloma ◽  
Second Primary Malignancies ◽  
Peripheral Sensory

Introduction: Proteasome inhibitors-based regimens are the mainstay of initial therapy for most patients with multiple myeloma. Daratumumab is a human IgGκ monoclonal antibody that targets CD38 with direct antitumor effects and has an immunomodulatory component. Recent studies have demonstrated that addition of daratumumab to standard regimens enhance direct cytotoxicity on myeloma cells and have shown survival benefits. Yet, there are notable safety concerns. We performed a combined analysis of randomized controlled trials (RCT) to determine the risk of second primary malignancies (SPM) and peripheral sensory neuropathy (PSN) with newer daratumumab combination regimens. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2019. Phase III RCTs utilizing daratumumab in patients with multiple myeloma that mention SPM and PSN as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Random effects model was applied. Results: A total of 3,547 patients with multiple myeloma from 5 phase III RCTs were eligible. Studies compared daratumumab (D) + bortezomib (V) + melphan (M) + prednisone (P) vs VMP, D + lenalidomide (R) + dexamethasone (d) vs Rd, DVd vs Vd and DVd + thalidomide (T) vs VTd. The randomization ratio was 1:1 in all studies. Daratumumab was utilized in relapsed and refractory multiple myeloma in the POLLUX study (n= 564) and the CASTOR study (n= 480) and as first-line treatment for patients with multiple myeloma in the ALCYONE study (n= 700), the CASSIOPEIA study (n= 1085) and the MAIA study (n= 737). The I2 statistic for heterogeneity was 25, suggesting some heterogeneity among RCT. The SPM incidence was 76 (4.29%) in study group vs 77 (4.34%) in control group. The RR for SPM was 1.12 (95% CI: 0.74 - 1.69; P = 0.58) and RD was 0.01 (95% CI: -0.01 to 0.02; P = 0.34). The RR for SPM was noted at 2.56 (95% CI: 0.26 - 25.46; P = 0.42) in a subset of relapsed and refractory multiple myeloma. Any-grade PSN was reported in 527 (46.84%) in daratumumab arm vs 550 (48.72%) in control arm with the RR of 0.98 (95% CI: 0.80 -1.21; P = 0.88). High-grade PSN was noted in 63 (5.6%) vs 76 (6.73%) in control group with the RR of 0.73 (95% CI: 0.42 -1.27; P = 0.27). Conclusions: Our meta-analysis depicted that there was no significant increase in the risk of second primary malignancies and peripheral sensory neuropathy in patients on daratumumab combination regimen, in newly diagnosed and relapsed refractory multiple myeloma, compared to control arm. However, long-term follow-up of these patients is required to determine the actual relation with second primary malignancies. Disclosures No relevant conflicts of interest to declare.

scholarly journals BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma

Blood ◽  
2013 ◽  
Vol 121 (11) ◽  
pp. 1982-1985 ◽  
Author(s):  
Adriana Rossi ◽  
Tomer Mark ◽  
David Jayabalan ◽  
Paul Christos ◽  
Faiza Zafar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Second Primary ◽  
Newly Diagnosed ◽  
Key Points ◽  
Second Primary Malignancies

Key Points Long-term lenalidomide/dexamethasone/biaxin in newly diagnosed myeloma is safe and effective. No increased incidence of second primary malignancies seen in lenalidomide without alkylators.

Risk of second malignancy in patients with ovarian clear cell carcinoma

2020 ◽  
pp. ijgc-2020-001946
Author(s):  
Julie My Van Nguyen ◽  
Danielle Vicus ◽  
Sharon Nofech-Mozes ◽  
Lilian T Gien ◽  
Marcus Q Bernardini ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Second Primary ◽  
Ovarian Clear Cell Carcinoma ◽  
Second Primary Malignancy ◽  
Primary Malignancy ◽  
Increased Risk ◽  
Second Primary Malignancies

ObjectiveOvarian clear cell carcinoma has unique clinical and molecular features compared with other epithelial ovarian cancer histologies. Our objective was to describe the incidence of second primary malignancy in patients with ovarian clear cell carcinoma.MethodsRetrospective cohort study of patients with ovarian clear cell carcinoma at two tertiary academic centers in Toronto, Canada between May 1995 and June 2017. Demographic, histopathologic, treatment, and survival details were obtained from chart review and a provincial cancer registry. We excluded patients with histologies other than pure ovarian clear cell carcinoma (such as mixed clear cell histology), and those who did not have their post-operative follow-up at these institutions.ResultsOf 209 patients with ovarian clear cell carcinoma, 54 patients developed a second primary malignancy (25.8%), of whom six developed two second primary malignancies. Second primary malignancies included: breast (13), skin (9), gastrointestinal tract (9), other gynecologic malignancies (8), thyroid (6), lymphoma (3), head and neck (4), urologic (4), and lung (4). Eighteen second primary malignancies occurred before the index ovarian clear cell carcinoma, 35 after ovarian clear cell carcinoma, and 7 were diagnosed concurrently. Two patients with second primary malignancies were diagnosed with Lynch syndrome. Smoking and radiation therapy were associated with an increased risk of second primary malignancy on multivariable analysis (OR 3.69, 95% CI 1.54 to 9.07, p=0.004; OR 4.39, 95% CI 1.88 to 10.6, p=0.0008, respectively). However, for patients developing second primary malignancies after ovarian clear cell carcinoma, radiation therapy was not found to be a significant risk factor (p=0.17). There was no significant difference in progression-free survival (p=0.85) or overall survival (p=0.38) between those with second primary malignancy and those without.ConclusionPatients with ovarian clear cell carcinoma are at increased risk of second primary malignancies, most frequently non-Lynch related. A subset of patients with ovarian clear cell carcinoma may harbor mutations rendering them susceptible to second primary malignancies. Our results may have implications for counseling and consideration for second primary malignancy screening.

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