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.

A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide

Blood ◽  
2012 ◽  
Vol 119 (12) ◽  
pp. 2764-2767 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Paul G. Richardson ◽  
Nancy Brandenburg ◽  
Zhinuan Yu ◽  
Donna M. Weber ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Pooled Analysis ◽  
Second Primary ◽  
Separate Analysis ◽  
Second Primary Malignancy ◽  
Primary Malignancy ◽  
Pivotal Phase ◽  
Refractory Multiple Myeloma ◽  
Skin Cancers ◽  
Second Primary Malignancies

Abstract In a retrospective pooled analysis of 11 clinical trials of lenalidomide-based therapy for relapsed/refractory multiple myeloma (MM; N = 3846), the overall incidence rate (IR, events per 100 patient-years) of second primary malignancies (SPMs) was 3.62. IR of invasive (hematologic and solid tumor) SPMs was 2.08, consistent with the background incidence of developing cancer. In a separate analysis of pooled data from pivotal phase 3 trials of relapsed or refractory MM (N = 703), the overall IR of SPMs was 3.98 (95% confidence interval [CI], 2.51-6.31) with lenalidomide/dexamethasone and 1.38 (95% CI, 0.44-4.27) with placebo/dexamethasone; IRs of nonmelanoma skin cancers were 2.40 (95% CI, 1.33-4.33) and 0.91 (95% CI, 0.23-3.66), respectively; IRs of invasive SPMs were 1.71 (95% CI, 0.86-3.43) and 0.91 (95% CI, 0.23-3.66), respectively. The risk of SPMs must be taken into account before initiating lenalidomide treatment. In the context of the observed survival benefit in relapsed or refractory MM patients, the benefit/risk profile of lenalidomide/dexamethasone remains positive.

The effect of bundle of warmth care for patients with advanced colorectal cancer undergoing chemotherapy on reduction of oxaliplatin-related peripheral sensory neuropathy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15031-e15031
Author(s):  
Jin-Xiang Lin ◽  
Zhan-hong Chen ◽  
Xiang-Wei Chen ◽  
Zu-Yan Fan ◽  
Xiu-Yan Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Intervention Group ◽  
Sensory Neuropathy ◽  
Warm Water ◽  
Control Group ◽  
Peripheral Sensory Neuropathy ◽  
Exposure To Cold ◽  
Hands And Feet ◽  
Peripheral Sensory

e15031 Background: FOLFOX is the one of the most selected chemotherapy regimens for advanced colorectal carcinoma (aCC) patients, which includes oxaliplatin, 5-fu and leucovorin. However, oxaliplatin often causes chemotherapy-induced peripheral sensory neuropathy (CIPN) which is a common treatment-related adverse effect and affects long- term quality of life. The aim of the study is to observe the effect of warmth intervention on patients with advanced colorectal cancer undergoing chemotherapy. Methods: A total of 60 aCC patients were recruited. They were randomized into an intervention group (30 patients) and a control group (30 patients). The intervention group accepted the bundle of warmth care which included wearing cotton gloves and socks, washing hands and taking a bath with warm water, soaking hands and feet before sleep with warm water, reducing exposure to cold and avoiding cold food. The control group was treated with conventional health education which including how to reduce exposure to cold. CTCAE-4.0 was used to evaluate patient, s peripheral sensory neuropathy at baseline, 3 months, 6 months and 6 months after chemotherapy terminate. Results: At baseline, there was no peripheral sensory neuropathy in two groups. In 3 months, incidence of peripheral sensory neuropathy of intervention group and control group were 26.67%(Ⅰ:20.00%,Ⅱ:6.67%) VS 83.34% (Ⅰ:46.67%,Ⅱ:30.00%,Ⅲ:6.67%)(χ2= 22.289,p = 0.000). In 6 months, incidence of peripheral sensory neuropathy of two group were 36.67% (Ⅰ: 26.67%,Ⅱ: 10.00%) VS 93.34%(Ⅰ:46.67%,Ⅱ:30.00%,Ⅲ:16.67%) (χ2= 23.398,p = 0.000). 6 months after chemotherapy terminate, incidence of peripheral sensory nerve damage of two group were 13.33%(Ⅰ:10.00%,Ⅱ:3.33%) VS 33.34%(Ⅰ:6.67%,Ⅱ:10.00%,Ⅲ:6.67%) (χ2= 4.283,p = 0.233). Conclusions: Bundle of warmth care reduced oxaliplatin-related peripheral sensory neuropathy on patients with advanced colorectal cancer undergoing chemotherapy.

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 Updated Meta-Analysis of Randomized Controlled Trials to Evaluate the Incidence of Infection and Pneumonia in Patients with Multiple Myeloma Treated with Daratumumab

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4771-4771
Author(s):  
Thura Win Htut ◽  
Aung M Tun ◽  
Anita Sultan ◽  
Myint Aung Win ◽  
Sriman Swarup ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Phase Iii ◽  
Control Group ◽  
Controlled Trials ◽  
Study Group ◽  
High Grade ◽  
Newly Diagnosed ◽  
Antitumor Effects ◽  
Randomized Controlled

Introduction: Multiple myeloma is a hematologic cancer of plasma cell, a blood cell which normally produce antibodies, and accounts for approximately 13% of all hematologic malignancies. Daratumumab is a human anti CD38 IgGκ monoclonal antibody with a well characterized mechanism of action via direct antitumor effects and an immunomodulatory component and the incorporation of daratumumab to standard multiple myeloma regimen has shown to significantly improve response rates and survival, with notable toxicities. We performed a combined analysis of randomized controlled trials (RCT) to determine the risk of infection and pneumonia in patients with multiple myeloma treated with daratumumab. 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 infection including pneumonia 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 35, suggesting some heterogeneity among RCT. The incidence of any-grade infection was 58.01% in study group vs 48.06 % in control group (RR, 1.21; 95% CI: 1.12 - 1.31; P < 0.0001). High-grade infection rate was 5.46% higher in daratumumab group compared to control arm (RR, 1.27; 95% CI: 1.13 - 1.44; P = 0.0001). Any-grade pneumonia was reported in 12.58% in study arm versus 7.72%% in control group with RR of 1.63 (95% CI: 1.08 - 2.45; P = 0.02). High-grade pneumonia was 8.47% in study group versus 5.52% in control arm (RR, 1.51; 95% CI: 0.97 - 2.35; P = 0.07). The RR for high-grade pneumonia was statistically significant at 2.07 (95% CI: 1.50 - 2.85; P < 0.0001) in a subset of newly diagnosed multiple myeloma patients treated with daratumumab (n= 2503). Conclusions: The addition of daratumumab to standard multiple myeloma regimen contributed to higher incidence of all grades of infection and any-grade pneumonia, with RR of 1.27 for high-grade infection and RR of 1.63 for any-grade pneumonia. However, high-grade pneumonia was only found to be significant in a subset of patients with newly diagnosed multiple myeloma treated with daratumumab, with RR of 2.07. Timely intervention with proper supportive care is required. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Outcome of Bortezomib Retreatment in Patients with Relapsed or Refractory Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jae-Sook Ahn ◽  
Sung-Hoon Jung ◽  
Seung-Shin Lee ◽  
Seo-Yeon Ahn ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Grade 3 ◽  
Peripheral Sensory ◽  
Good Partial Response

This retrospective study investigated the clinical efficacy and safety of bortezomib retreatment in patients with relapsed or refractory multiple myeloma (MM). A total of 30 patients who relapsed or progressed after≥6 months since the last dose of their previous bortezomib therapy were included in this study. During the median 6 cycles (range: 2–12) of bortezomib retreatment, 10 (33.3%), 2 (6.7%), and 6 (20.0%) patients achieved complete response, very good partial response, and partial response, respectively. Grade 3 or 4 neutropenia (47.0%), thrombocytopenia (43.0%), anemia (10.0%), and peripheral sensory neuropathy (3.0%) were observed. The median time to progression, progression-free survival, and overall survival were 5.8 months (95% CI: 2.6–9.0), 5.5 months (95% CI: 4.2–6.8), and 13.4 months (95% CI: 6.1–20.7), respectively. Patients who received bortezomib retreatment≥12 months from initial last therapy had a 1-year OS rate of 65.8% (95% CI: 43.5–88.1) while patients receiving retreatment after 6–12 months interval had a 1-year OS rate of 41.7% (95% CI: 13.9–69.5) (P=0.038). In conclusion, this study demonstrates that retreatment with bortezomib is an effective strategy for patients with MM who relapsed at a long interval after initial bortezomib therapy.

scholarly journals Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial

2019 ◽  
Vol 37 (7) ◽  
pp. 589-597 ◽  
Author(s):  
Edward A. Stadtmauer ◽  
Marcelo C. Pasquini ◽  
Beth Blackwell ◽  
Parameswaran Hari ◽  
Asad Bashey ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hematopoietic Cell Transplantation ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Complete Response ◽  
Drug Regimen ◽  
Initial Therapy ◽  
Phase Iii ◽  
Second Primary ◽  
Second Primary Malignancies

PURPOSE Single-cycle melphalan 200 mg/m2 and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression. PATIENTS AND METHODS Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS. RESULTS The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms. CONCLUSION Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.

scholarly journals Tolerability in Patients with Multiple Myeloma Treated with Daratumumab: A Systematic Review and Meta-Analysis of Phase III Randomized Controlled Trials

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1873-1873 ◽  
Author(s):  
Thura Win Htut ◽  
Myint Aung Win ◽  
Sriman Swarup ◽  
Anita Sultan ◽  
Nimesh Adhikari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Proteasome Inhibitors ◽  
Phase Iii ◽  
Control Group ◽  
Combination Regimen ◽  
Antitumor Effects ◽  
Significant Difference

Introduction: Multiple myeloma, which accounts for 1% of all cancers, is a hematologic cancer in which clonal plasma-cell proliferation leads to complications and death. Over the recent years, it has shown that the introduction of novel agents, including daratumumab and the incorporation of proteasome inhibitors and immunomodulatory drugs has improved outcomes in patients with multiple myeloma. Daratumumab is a human, CD38-targeting, IgG1κ monoclonal antibody with direct antitumor effects and an immunomodulatory component and has recently shown to improve survival in patients with multiple myeloma. However, there are considerable safety concerns. The purpose of our study is to determine the risk of TD and deaths due to treatment-related adverse events (TRAE) in patients with multiple myeloma treated with daratumumab. 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 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: Five phase III RCTs with a total of 3,547 patients with multiple myeloma were eligible. Studies compared daratumumab (D) + bortezomib (V) + melphan (M) + prednisone (P) vs VMP, D + lenalidomide (R) + dexamethasone (d) vs Rd, DVd vs Vd, DVd + thalidomide (T) vs VTd and DRd vs Rd. 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 39, suggesting some heterogeneity among RCTs. TD due to TRAE was noted in 120 (6.77%) vs 179 (10.08%) in control group with RR of 0.68 (95% CI: 0.51 -0.91; P = 0.0009) and RD of -0.03 (95% CI: -0.06 to 0.00; P = 0.02). TD due to infection/ pneumonia was reported in 0.95% vs 0.73% in control group (RR, 1.19; 95% CI: 0.42 -3.34; P = 0.75). Treatment-related deaths were 64 (3.61%) in daratumumab arm vs 77 (4.34%) in control arm. The pooled RR was not statistically significant at 0.86 (95% CI: 0.59 -1.25; P = 0.43). Conclusions: The rate of discontinuation of trial treatment due to adverse events was significantly lower in the daratumumab group (6.77%) than in the control arm (10.08%) with RR of 0.68, favoring daratumumab combination regimen. Furthermore, there was no significant difference in the treatment discontinuation due to pneumonia or infection and treatment-related deaths due to TRAE in the daratumumab group, compared to control arm. Disclosures No relevant conflicts of interest to declare.

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