Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3557-3560 ◽  
Author(s):  
Paul G. Richardson ◽  
Pieter Sonneveld ◽  
Michael Schuster ◽  
David Irwin ◽  
Edward Stadtmauer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Single Agent ◽  
Response Duration ◽  
Proteasome Inhibition ◽  
Initial Response ◽  
Complete Response ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Protein Reduction

AbstractInitial analysis of the Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of relapsed multiple myeloma patients showed significantly longer time to progression, higher response rate, and improved survival with single-agent bortezomib versus high-dose dexamethasone. In this updated analysis (median follow-up: 22 months), survival was assessed in both arms, and efficacy updated for the bortezomib arm. Median survival was 29.8 months for bortezomib versus 23.7 months for dexamethasone, a 6-month benefit, despite substantial crossover from dexamethasone to bortezomib. Overall and complete response rates with bortezomib were 43% and 9%, respectively; among responding patients, 56% improved response with longer therapy beyond initial response, leading to continued improvement in overall quality of response. Higher response quality (100% M-protein reduction) was associated with longer response duration; response duration was not associated with time to response. These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy. This study is registered at http://clinicaltrials.gov (Study ID NCT00048230).

Bortezomib Continues Demonstrates Superior Efficacy Compared with High-Dose Dexamethasone in Relapsed Multiple Myeloma: Updated Results of the APEX Trail.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2547-2547 ◽  
Author(s):  
Paul Richardson ◽  
P. Sonneveld ◽  
M. Schuster ◽  
D. Irwin ◽  
E. Stadtmauer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Single Agent ◽  
Response Rates ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Duration Of Response ◽  
Clinical Benefits ◽  
Grade 3

Abstract Introduction: In the international, multicenter phase 3 APEX trial, 669 patients (pts) with multiple myeloma (MM) who had relapsed after 1–3 prior therapies were randomized to receive bortezomib (VELCADE®) 1.3 mg/m2 IV d 1, 4, 8, 11 q3wk for 8 cycles followed by 3 cycles on d 1, 8, 15, 22 q5wk, or dexamethasone (Dex) 40 mg PO d 1–4, 9–12, 17–20 q5wk for 4 cycles followed by 5 cycles on d 1–4 q4wk. Pts refractory to Dex were excluded, and those with progressive disease on Dex were eligible to cross over to bortezomib. Pts receiving bortezomib achieved significant improvement in time to progression (TTP, primary end point), response rate (CR + PR using EBMT criteria), and survival (Richardson. NEJM.2005;352:2487), which resulted in early closure of the trial. The duration of response (DOR) was longer with bortezomib, and infections ≥ grade 3, time to skeletal events, grade 4 adverse events (AE), serious AE, and discontinuations due to AE were similar in the 2 treatment arms. Methods: In this analysis, updated response rates, time to response (TTR), DOR, survival, and TTP are presented after extended follow-up. A matched-pairs analysis comparing survival and TTP of pts on bortezomib in APEX with those in another trial of MM pts who received bortezomib after Dex will also be presented. Results: 669 pts received a median of 7 cycles of therapy. Based on a median follow-up of 15.8 months, the median TTP, 1-year and overall survival (OS), response rates, median TTR, and median DOR for pts receiving bortezomib are shown in the table. Median duration of therapy for responders (CR + PR) was 7.2 months. Improved response with longer therapy (after cycle 6) was observed in 76 pts (56% of responders) in the bortezomib arm (20 pts improved from MR or PR to CR, and 56 pts improved from MR to PR). Furthermore, 28 of 135 responders (21%) achieved first response (CR/PR) after cycle 4, including 18 pts (13%) on or after cycle 6, and 10 pts (7%) on or after cycle 8. OS increased substantially with more follow-up. Median TTR was more rapid, and median DOR was longer in pts achieving CR and near CR than in those with PR. Conclusion: Updated TTP, response rates, survival, TTR, and DOR for the bortezomib group continue to support the findings of the original analysis. Thus, the clinical benefits of single-agent bortezomib in pts with relapsed MM remain robust after extended follow-up, supporting its early use in relapsed MM and its further study in the treatment of newly diagnosed disease. Efficacy Bortezomib (n = 333) Median TTP, mo 6.2 1-year survival, % 80 Median OS, mo 25.4 Response rate, % (n/N) 43 (135/315) CR 9 (27/315) PR 34 (108/315) -near CR 7 (21/315) Median TTR, mo (range) 1.4 (0.5–6.0) CR 0.8 (0.5–4.0) PR 1.4 (0.5–6.0) -near CR 0.8 (0.6–2.4) Median DOR, mo 7.8 CR 9.9 PR 7.6 -near CR 11.5

Initial Results of PX-171-003, An Open-Label, Single-Arm, Phase II Studyof Carfilzomib (CFZ) in Patients with Relapsed and Refractory Multiple Myeloma (MM)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 864-864 ◽  
Author(s):  
Sundar Jagannath ◽  
Ravi Vij ◽  
A. Keith Stewart ◽  
George Somlo ◽  
Andrzej Jakubowiak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 1 ◽  
Single Agent ◽  
Proteasome Inhibition ◽  
Complete Response ◽  
Open Label ◽  
Upper Respiratory Infection ◽  
Heavily Pretreated ◽  
Clinical Benefit Response ◽  
High Level

Abstract Background: Carfilzomib (CFZ) is a novel proteasome inhibitor of the epoxyketone class that exhibits a high level of selectivity for the proteasome and has been shown in a phase 1 study to result in greater than 80% proteasome inhibition on a QDx2 consecutive day schedule. We piloted this agent in MM patients with relapsed and refractory disease, who had failed bortezomib (BTZ) and at least one immunomodulatory (IMiD) agent, e.g., thalidomide (THAL) and/or lenalidomide (LEN). Methods: PX-171-003 is an open-label, multicenter study enrolling pts with MM who have relapsed from at least 2 prior therapies and who are refractory; defined as progressing on or within 60 days of last therapy or<25% response to the last therapy. Pts received CFZ 20 mg/m2 IV Days 1, 2, 8, 9, 15 and 16 every 28 days, for up to 12 cycles. Dexamethasone 4 mg po was administered prior to each dose in Cycle 1. Responses were evaluated by the International Uniform Response Criteria for Multiple Myeloma. Clinical benefit response (CBR) was defined as complete response (CR) + partial/very good partial response (PR/VGPR) + minimal response (MR, as defined by EBMT criteria). Responses were adjudicated by an independent review committee. Results: 46 pts were enrolled, including 78% with progression on or within 60days of last therapy and 22% with no response to last therapy. 39 pts initiated treatment, completed at least one cycle of CFZ, had measurable M-protein, and were evaluable (eval) for response. The mean number of prior therapies (excluding transplant) was 6.4(range 1 to 18). 100% of pts received prior BTZ, 91% prior THAL, 89% prior LEN, and 83% prior stem cell transplantation (SCT). To date, pts received a median of 3 cycles(range 1–9) of CFZ; 22 started at least 4 cycles. The CBR was 26% (10/39 eval pts), including 5 pts achieving PR, 5 pts achieving MR, and 16 additional patients achieving stable disease (SD). Time to response was rapid, frequently occurring in the 1st cycle. CFZ was generally well tolerated; the most common adverse events (AEs) were fatigue(65%), nausea (37%), upper respiratory infection (37%), and diarrhea (33%). Worsening of hematologic parameters: anemia (65%); thrombocytopenia (46%) and neutropenia(20%) were predominantly Grades 1 and 2. Increased creatinine, both drug and non-drug related, was seen in 15/46 pts (33%), but treatment was discontinued in only 3 patients due to a renal adverse event. Acute renal failure was documented in 4 pts (9%), 2 (4%) of whom also had possible tumor lysis. 78% of pts had Grade 1 or 2 peripheral neuropathy (PN) at baseline. Exacerbation of PN was rare, and there were no study discontinuations or dose reductions due to PN. Conclusions: In the context of this heavily pre-treated MM population, single agent CFZ was able to induce CBR in 26% of MM patients, the majority of whom had failed BTZ, LEN, THAL, and SCT. CFZ was generally well-tolerated, and toxicities were manageable. Importantly, exacerbation of pre-existing PN was rare and did not result in dose reduction or discontinuation of therapy. These observations support further evaluation of CFZ as a promising new agent in MM. Enrollment is proceeding at an escalated dose (based on tolerability) in this trial. Additional studies of CFZ in patients who are less heavily pretreated and in combination with other chemotherapy agents are ongoing.

scholarly journals CENTRAL NERVOUS SYSTEM RELAPSE OF MULTIPLE MYELOMA

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Maria Qubtia ◽  
Muhammad Umer Nasir ◽  
Memoona Mian ◽  
Abdul Hameed
Keyword(s):  
Central Nervous System ◽  
Multiple Myeloma ◽  
Nervous System ◽  
Initial Response ◽  
Complete Response ◽  
Neurological Status ◽  
Best Supportive Care ◽  
High Dose ◽  
Central Nervous System Relapse ◽  
Dismal Prognosis

Multiple myeloma (MM) is a plasma cell disorder primarily involving bone marrow. Extramedullary involvement is less common, with central nervous system (CNS) myelomatosis being a rare entity and such presentation carries extremely dismal prognosis. We present case of a 40 years old male with MM who was initially treated with 6 cycles of Cyclophosphamide, Thalidomide and Dexamethasone resulting in complete response. 2 years later he presented with CNS myelomatosis and scrotal involvement and was initially treated with Bortezomib and dexamethasone, cranial irradiation and intrathecal Methorexate, Cytarabine, Hydrocortisone (TRIO IT), along with radical orchiectomy and testicular radiation during the course of treatment. However, after initial response his disease showed clinical and radiological progression after 4 months of therapy. He was switched to high dose Methotrexate (HD-MTX) with TRIOITand later Lenalidamide and dexamethasone (Len/dex) was added to the above regimen. He continued to show good clinical response but his cytology remained persistently positive, therefore, HD-MTX was discontinued in the later course of treatment. Subsequently he was started on best supportive care only, when his neurological status deteriorated further. He survived almost 9 months after a diagnosis of CNS myelomatosis. Patients with multiple myeloma, presenting with neurological symptoms should always be investigated for the possibility of CNS MM. CNS relapse is a fatal disease with poor prognosis. Recommended treatment must include a systemic anti-MM regimen that crosses the BBB (ideally Immunomodulatory drugs (IMiDs) IMiDs-dexamethasone based therapy), CNS irradiation and intrathecal chemotherapy.Key words: Multiple myeloma, central nervous system myelomatosis, therapy

scholarly journals Eltrombopag, Low-Dose Rituximab, and High-Dose Dexamethasone Combination for Patients with Newly Diagnosed Immune Thrombocytopenia: A Pilot "Total Therapy" Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1369-1369
Author(s):  
David Gomez-Almaguer ◽  
Olga Cantu-Rodriguez ◽  
Cesar Homero Gutierrez-Aguirre ◽  
Jose Carlos Jaime-Perez ◽  
Luz C. Tarin-Arzaga ◽  
...  
Keyword(s):  
Partial Response ◽  
Board Of Directors ◽  
Low Dose ◽  
Complete Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
High Dose Dexamethasone ◽  
Frontline Therapy

Abstract Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder that results from platelet destruction and production suppression. Frontline-therapy includes corticosteroids, intravenous immune globulin or anti-D immunoglobulin. Single-agent treatments have not been successful in inducing prolonged remission, as relapse will occur in approximately 50% of patients. Low-dose rituximab (100 mg) has been used for the treatment of ITP, showing an activity almost similar to the 375 mg/m2 standard dose. We and others have reported sustained response rates ranging from 58% to 76% using rituximab plus dexamethasone as a frontline therapy. Eltrombopag is a thrombopoietin nonpeptide mimetic that has been shown to raise platelet count in chronic ITP, and we have previously reported eltrombopag/dexamethasone as a feasible frontline therapy for ITP reaching 100% response rates.The lack of sustained response in many adult patients with newly diagnosed acute ITP has stimulated the search for a treatment that modifies the natural course of the disease. Objetive: We aim to evaluate efficacy, safety, and response duration of low-dose weekly rituximab (100 mg weekly, four doses) plus high-dose dexamethasone (40 mg PO, days 1-4) in combination with eltrombopag (50 mg, days 1-28) as frontline therapy in newly diagnosed primary ITP in an ambulatory setting. Methods: This is an ongoing open-label, single-arm study performed in patients with newly diagnosed ITP from the Hospital Universitario Dr. Jose Eleuterio Gonzalez in Monterrey, Mexico (Clinical trials.gov NCT02834286). Eligible patients are 16 years or older, with bleeding manifestations and/or a platelet count ²30×109/L, without previous treatment. Patients are excluded if they had active infection, pregnancy, or a malignant disease. A complete blood count is performed at baseline, on days 3, 5, 7 and then weekly for 28 days, monthly until month 6, and every 3 months thereafter. Partial and complete responses are defined as an increase in platelet counts ³30×109/L and ³100×109/L, respectively. Results: Ten consecutive patients have been enrolled from March 2015 until July 2016. Median age was 37 years (16-61). Six patients were women (60%) and four were men (40%). Median platelet account at diagnosis was 7 « 109/L (range 1.2-28). Median follow-up has been 7 months (range 1-13). All patients achieved at least a partial response (PR) at a median of 4 days (range 3-14). Complete response (CR) was achieved in 9 patients in a median of 7 days (7-22); all of them were still in CR at the end of treatment (Day 28). One patient lost response at 28 days and received a second high-dexamethasone course maintaining CR. No significant adverse effects have occurred during treatment, only 1 patient reported mild myalgia. No relapses have been documented until now.Currently, 8 patients remain in CR and 2 in PR. Conclusion:This is the first trial evaluating the response of low-dose rituximab in combination with eltrombopag and high-dose dexamethasone in newly diagnosed patients with ITP.Low-dose rituximab in combination with eltrombopag and high dose dexamethasone is a feasible frontline therapy for ITP. This drug combination showed high response rates achieved very rapidly, with a low incidence of side effectsand might represent an attractive option in patients with ITP and substantial bleeding. Table Characteristics and follow-up of patients M: Male, F: Female, CR: Complete Response, PR: Partial Response Table. Characteristics and follow-up of patients. / M: Male, F: Female, CR: Complete Response, PR: Partial Response Disclosures Gomez-Almaguer: Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Romiplostim, Low-Dose Rituximab and High-Dose Dexamethasone Combination in Newly Diagnosed Immune Thrombocytopenia: Another "Total Therapy" Pilot Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1014-1014
Author(s):  
Perla R. R. Colunga-Pedraza ◽  
Mónica Bustillos Muñoz ◽  
Fernando De La Garza ◽  
Andres Gomez-De Leon ◽  
Edgar Ulises Coronado-Alejandro ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Initial Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Front Line ◽  
High Dose Dexamethasone ◽  
Line Therapy ◽  
Total Therapy

Abstract Background: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that results from accelerating platelet clearance, destruction, and production. Front-line therapy for newly diagnosed ITP includes corticosteroids, intravenous immune globulin, or anti-D immunoglobulin. However, after these single-agent therapies, relapses will occur in half of patients. We previously reported the safety, feasibility, and efficacy of the combination of dexamethasone, low-dose rituximab, and the thrombopoietin receptor agonist (TPO-Ra) eltrombopag as front-line treatment in newly diagnosed ITP. Romiplostim, another TPO-Ra is approved by the FDA for patients with chronic ITP. However, the safety, tolerability, and efficacy of romiplostim combined with low-dose rituximab, and high-dose dexamethasone in newly diagnosed ITP remain unknown. Objective: Our primary objectives were safety, and tolerability. Secondary objectives were initial response and relapse incidence. Methods: An open-label, single-arm study was performed in Hospital Universitario "Dr. José Eleuterio González" in Monterrey, Mexico (Clinical trials.gov NCT04588194). Eligible patients were newly diagnosed ITP patients, treatment-naïve, ≥18 years, with a platelet count ≤30×10 9/L. Patients were excluded if they had an active infection, pregnancy, or malignant disease. The treatment regimen was romiplostim (2 mcg/kg weekly, four doses), low-dose rituximab (100 mg weekly, four doses) and high-dose dexamethasone (40 mg PO, days 1-4). Dexamethasone was allowed up to 3 cycles. Partial (PR) and complete responses (CR) were defined as an increase in platelet counts ≥30×10 9/L (at least a doubling of the baseline count) and ≥100×10 9/L, respectively. Results: We included ten consecutive patients. The median age was 34.5 years (range, 17-63). Seven patients were men (70%). The median platelet account at diagnosis was 6x10 9/L (range 0-23), and median follow-up was 180 days (range 30-270). The median number of romiplostim doses was 3.5 (range 1-4), and three (30%) patients required dose adjustment due to thrombocytosis. All but one patient achieved response (CR or PR) at a median of 7 days (range 7-28). Five patients (50%) achieved CR at 28 days of treatment, and four patients (40%) PR. No significant adverse effects have occurred during treatment; one patient presented grade 1 myalgia and the other a grade 2 soft tissue infection. Five patients (50%) relapsed during follow-up. Recently, four (40%) patients remain in CR and three (30%) in PR. Conclusion: The combination of romiplostim, low-dose rituximab, and high-dose dexamethasone was safe and effective. This "total therapy" approach was associated with minimum side effects and rapid initial response. Prospective validation in a larger sample is needed. Figure 1 Figure 1. Disclosures Gomez-Almaguer: Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. OffLabel Disclosure: Romiplostim in firs-line therapy for immune thrombocytopenia

Relationship between Quality of Response to Bortezomib (btz) and Clinical Benefit in Multiple Myeloma (MM) in the APEX and SUMMIT Studies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3529-3529 ◽  
Author(s):  
Ruben Niesvizky ◽  
P.G. Richardson ◽  
P. Sonneveld ◽  
M.W. Schuster ◽  
M. Coleman ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Response Rate ◽  
Alternative Therapy ◽  
Single Agent ◽  
Initial Response ◽  
High Dose ◽  
Mass Reduction ◽  
Tumor Mass ◽  
High Dose Dexamethasone

Abstract BACKGROUND: The phase 2 SUMMIT trial of patients (pts) with relapsed and refractory MM showed that btz (VELCADE®) is active, with a response rate of 27% (CR/PR) as a single agent, median TTP of 7 months, and median OS of 17 months. The phase 3 APEX trial in pts with relapsed MM following 1–3 prior therapies showed btz to be superior to high-dose dexamethasone (dex) in terms of response rate, TTP, and OS. Updated APEX data show a CR/PR rate of 43%, median TTP of 6.2 months, and median OS of 29.8 months. This analysis evaluated the relationship between quality of response to btz (CR/nCR versus PR; PR does not include nCR in this analysis) in these trials and clinical benefit, as defined by treatment-free interval and time-to-alternative-therapy (TFI and TTAT; time from last and first dose of btz, respectively, to first dose of alternative antineoplastic therapy), OS, and TTP. METHODS: In SUMMIT, 202 pts received btz 1.3mg/m2 on days 1, 4, 8, and 11 for up to eight 21-day cycles (median # of cycles: 6). Dex 20mg was added on the day of and day after each btz dose in pts with suboptimal responses to btz alone. In one arm of APEX, 333 pts received btz 1.3mg/m2 on days 1, 4, 8, and 11 for eight 3-week cycles and then on days 1, 8, 15, and 22 for three 5-week maintenance cycles (median # of cycles: 6). Responses in both trials were assessed according to EBMT criteria (modified to include nCR, a CR with positive immunofixation test). RESULTS: Data are shown in the Table. Median TFI appeared longer in pts with CR/nCR vs PR (SUMMIT, 9.8 vs 3.1 months; APEX, 17.5 vs 6.7 months). Similarly, TTAT appeared longer in pts with CR/nCR vs PR (SUMMIT, 15.4 vs 8.5; APEX, 21.2 vs 14.0). Median OS in all response groups has not yet been reached after a median follow-up of 22 months. TTP tended to be longer with CR/nCR vs PR in both studies (SUMMIT, 16.4 vs 9.2; APEX, 12.2 vs 8.3). CONCLUSIONS: Increasing quality of response to btz is associated with greater clinical benefit assessed by extended TFI ,TTAT, and TTP. Long un-maintained remissions can be attained with btz by achieving maximum tumor mass reduction (CR/nCR), even in pts with relapsed/refractory MM. Updated APEX data show that despite rapid initial response, many pts showed continued improvement in terms of M-protein reduction, and an increasing proportion of pts achieved CR with continued therapy. These data, together with the findings of this analysis, support maximizing tumor mass reduction to CR/nCR with btz to achieve greater clinical benefit. Clinical benefit of btz by response Kaplan-Meier median (95% CI) CR/nCR PR* *PR does not include nCR in this analysis; †Includes 8 cycles of protocol-specified therapy plus maintenance cycles SUMMIT, n 19 34 TFI, mo 9.8 (2.7,14.3) 3.1 (2.0,8.7) TTAT, mo 15.4 (7.9,17.6) 8.5 (7.3,14.0) TTP, mo 16.4 (10.6,NE) 9.2 (7.2,NE) Median cycles, n 8 8 APEX, n 48 87 TFI, mo 17.5 (6.7,24.1) 6.7(4.4,10.0) TTAT, mo 21.2 (14.0,27.1) 14.0 (12.6,16.1) TTP, mo 12.2 (8.8,NE) 8.3 (7.6,10.3) Median cycles,† n 9 10

Bortezomib and Vorinostat Therapy as Maintenance Therapy after Autologous Transplant for Multiple Myeloma

2019 ◽  
Vol 143 (2) ◽  
pp. 146-154
Author(s):  
Leona A. Holmberg ◽  
Damian Green ◽  
Edward Libby ◽  
P.S. Becker
Keyword(s):  
Multiple Myeloma ◽  
Randomized Study ◽  
Single Agent ◽  
Survival Rates ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
High Dose Melphalan ◽  
Additional Therapy

Background: In multiple myeloma (MM), relapse is a frequent complication after autologous hematopoietic stem cell transplant (ASCT). To reduce the risk of relapse, additional therapy has been added post-ASCT. In a nontransplant relapse setting, the combination of intravenous bortezomib and oral vorinostat (BV) was studied and showed efficacy. Therefore, it was reasonable to study this combination therapy post-ASCT. Patients and Methods: We report on BV given post-ASCT. All 30 patients underwent conditioning for ASCT with high-dose melphalan. After recovery from the acute transplant-related toxicity, BV therapy was started and given for a total of 12 (28-day) cycles. Results: The most common toxicities were hematological, gastrointestinal (diarrhea and nausea), fatigue, and peripheral neuropathy. The median follow-up for BV patients is 7.8 (range: 6.12–9.03) years. After BV therapy, 18 patients (60%) are alive, and 9 (30%) are alive without disease progression. Conclusions: BV can be given post-ASCT with an acceptable toxicity profile and produces reasonable disease-free and overall survival rates. A randomized study comparing the BV regimen to single-agent lenalidomide or bortezomib is needed.

scholarly journals Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN

2021 ◽  
Vol 5 (4) ◽  
pp. 1092-1096
Author(s):  
Peter M. Voorhees ◽  
Cesar Rodriguez ◽  
Brandi Reeves ◽  
Nitya Nathwani ◽  
Luciano J. Costa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Survival Rates ◽  
Final Analysis ◽  
Complete Response ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Best Response

Abstract The phase 2 GRIFFIN study of daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) for transplant-eligible, newly diagnosed multiple myeloma included a safety run-in phase followed by a randomized phase. The ongoing randomized phase has met its prespecified primary end point of an improved stringent complete response (sCR) rate after consolidation for D-RVd (reported elsewhere). Final analysis of the safety run-in cohort is reported herein and provides longer follow-up (median, 40.8 months) encompassing daratumumab plus lenalidomide (D-R) maintenance therapy. Patients in the safety run-in cohort (N = 16) received 4 induction cycles (D-RVd), high-dose melphalan supported by autologous stem cell transplant, 2 consolidation cycles (D-RVd), and 24 months of maintenance (D-R). By the end of consolidation, all patients had responded, with a best response of sCR in 9 (56.3%) patients; 8 (50.0%) patients were minimal residual disease (MRD) negative (10‒5 threshold). After maintenance, 15 (93.8%) patients had achieved a best response of sCR, and 13 (81.3%) patients were MRD (10‒5) negative. Estimated 36-month progression-free and overall survival rates were 78.1% and 93.8%, respectively. One death from progressive disease occurred in the patient who did not achieve sCR. Observed safety profiles were consistent with daratumumab and RVd. With &gt;3 years of median follow-up, D-RVd achieved durable responses that deepened with D-R maintenance. This study was registered at www.clinicaltrials.gov as #NCT02874742.

Bortezomib Demonstrates Superior Efficacy to High-Dose Dexamethasone in Relapsed Multiple Myeloma: Final Report of the APEX Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1479-1479 ◽  
Author(s):  
Paul Richardson ◽  
P. Sonneveld ◽  
M. Schuster ◽  
D. Irwin ◽  
E. Stadtmauer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Randomized Study ◽  
Single Agent ◽  
Hazard Ratio ◽  
High Dose ◽  
Final Report ◽  
High Dose Dexamethasone ◽  
Duration Of Response ◽  
Overall Survival Benefit

Abstract Introduction/Methods: This international phase 3 study conducted at 93 sites is the largest randomized study to date in relapsed multiple myeloma (MM). Patients (pts) had to have received 1–3 prior therapies and those with dexamethasone (Dex) refractory disease were excluded. Pts were randomized to bortezomib (VELCADE®) 1.3 mg/m2 IV d 1, 4, 8, 11 q3wk for 8 cycles followed by 3 cycles on d 1, 8, 15, 22 q5wk, or Dex 40 mg PO d 1–4, 9–12, 17–20 q5wk for 4 cycles followed by 5 cycles on d 1–4 every 28 d. The 1° endpoint was time to progression (TTP); 2° endpoints included survival, response rate (CR+PR) using EBMT criteria, duration of response, time to response (TTR), time to skeletal events, infections ≥gr 3 and safety; exploratory endpoints included pharmacogenomics and quality of life. Pts with progressive disease on Dex were eligible to crossover to bortezomib in a companion study. Results: 669 pts were randomized and baseline characteristics were balanced in both arms. Based on a median follow-up of 8.3 mo, bortezomib demonstrated a 78% improvement in median TTP (hazard ratio 0.55, P<0.0001) and a significant 1-y and overall survival benefit over Dex (hazard ratio 0.53, P=0.0005; hazard ratio 0.57, P=0.0013, respectively). The response rate (CR+PR) was significantly higher (P<0.0001) with CR/nCR rates of 13% for bortezomib vs 2% for Dex. 132 (40%) and 119 (35%) pts received bortezomib or Dex 2nd line, respectively. Importantly, in 2nd-line bortezomib vs Dex, median TTP was 7.0 v 5.6 mo, 1-y survival was 89% vs 72%, and CR+PR rate was 45% vs 26%, respectively. The incidence of ≥ gr 3 adverse events and the discontinuation rate were similar across treatments in all pts. Conclusion: This is the first and largest randomized study demonstrating a survival advantage in relapsed MM, with single-agent bortezomib proving superior to Dex based on TTP, survival, and response. Superiority was also observed in 2nd line and later salvage therapy. The safety profiles of bortezomib and Dex were predictable and toxicities were manageable. Efficacy Bortezomib Dex P (n=333) (n=336) NC = not calculated. Median TTP, mo 6.2 3.5 <0.0001 1 prior line 7.0 (n=132) 5.6 (n=119) 0.0021 > 1 prior line 4.9 (n=200) 2.9 (n=217) <0.0001 1-year survival, % 80 66 0.0005 1 prior line 89 72 0.0098 > 1 prior line 73 62 0.0109 CR, % (n/N) 6 (20/315) 1 (2/312) 0.0001 1 prior line 6 (8/128) 2 (2/110) 0.0842 > 1 prior line 6 (12/187) 0 (0/202) 0.0002 CR/PR, % (n/N) 38 (121/315) 18 (56/312) <0.0001 1 prior line 45 (57/128) 26 (29/110) 0.0035 > 1 prior line 34 (64/187) 13 (27/202) <0.0001 Median TTR (CR/PR), d 43 43 NC

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