Analysis of efficacy and safety of POM as a replacement therapy for lenalidomide for relapsed/refractory multiple myeloma pts refractory to a lenalidomide-containing combination regimen.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19528-e19528
Author(s):  
James R. Berenson ◽  
Alexa Cohen ◽  
Tanya M. Spektor ◽  
Ashkan Lashkari ◽  
Roy Mackintosh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Replacement Therapy ◽  
Randomized Study ◽  
Combination Regimen ◽  
Phase 2 ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Phase 2 Trial ◽  
Previous Regimen

e19528 Background: Pomalidomide (POM) is a third –generation immunomodulatory drug shown to be safe and effective for the treatment of relapsed/refractory multiple myeloma (RRMM) for patients (pts) previously treated with bortezomib and lenalidomide (LEN) and in combination with dexamethasone it has been shown to overcome resistance in RRMM. In this phase 2 trial, we are evaluating the efficacy, safety and tolerability of POM as a replacement therapy for LEN for pts who have progressed receiving a LEN combination regimen. Methods: This is a phase 2, multicenter, open-label and non-randomized study. Pts who have failed a combination regimen containing LEN were treated with POM along with all of the other drugs previously used in the regimen. POM administered orally (dose is determined based on the previous regimen) on days 1-21 of a 28-day cycle, whereas other drugs are administered using the same schedule(s), dose(s) and drug combination as the last LEN-containing regimen that the patient received and failed. The planned enrollment on the study will be 45 pts. Results: To date, a total of 29 pts have been enrolled, 25 pts are evaluable and 12 pts have discontinued treatment. Of the evaluable pts, 9 (36%) and 16 (64%) received 3mg and 4mg of POM, respectively. The median age of all pts was 72 years (range, 52-81), and 17 (68%) were males. Pts have received a median of 3 prior treatments (range, 1-7). The median follow-up time for all pts is 3.1 months (range, 0.2-8.1). Amongst evaluable pts, 5 (23.8%) pts achieved at least a minimal response, 10 (47.6%) pts showed stable disease while 6 (28.6%) pts exhibited disease progression. At the time of data cutoff, only 17 pts have completed more than 1 full cycle of treatment; and, thus, the overall response and clinical benefit rates are fairly low (14.3% and 23.8%, respectively) but expected to improve with further follow up. The median PFS for the cohort was 7.6 months. Common ≥ Gr3 adverse events were neutropenia (8%), hypomania (4%) and leukopenia (4%). Conclusions: We show thatPOM appears to be promising replacement therapy for LEN in RRMM pts who have progressed within receiving a LEN combination regimen.

scholarly journals Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial

The Lancet ◽  
2016 ◽  
Vol 387 (10027) ◽  
pp. 1551-1560 ◽  
Author(s):  
Sagar Lonial ◽  
Brendan M Weiss ◽  
Saad Z Usmani ◽  
Seema Singhal ◽  
Ajai Chari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 2 ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Phase 2 Trial ◽  
Treatment Refractory

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study

2020 ◽  
Vol 21 (2) ◽  
pp. 207-221 ◽  
Author(s):  
Sagar Lonial ◽  
Hans C Lee ◽  
Ashraf Badros ◽  
Suzanne Trudel ◽  
Ajay K Nooka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 2 ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Phase 2 Study ◽  
Open Label Phase

scholarly journals Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results

2018 ◽  
Vol 180 (6) ◽  
pp. 821-830 ◽  
Author(s):  
Paul G. Richardson ◽  
William I. Bensinger ◽  
Carol Ann Huff ◽  
Caitlin L. Costello ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 2 ◽  
Refractory Multiple Myeloma ◽  
Phase 2 Trial

scholarly journals Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000798
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Wei Guo ◽  
Jin Gu ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
High Grade Osteosarcoma

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

scholarly journals Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Leukemia ◽  
2020 ◽  
Vol 34 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Meletios A. Dimopoulos ◽  
Darrell J. White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Intent To Treat ◽  
Line Of Therapy

Abstract In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

scholarly journals Extended follow-up of a phase 2 trial of bortezomib alone and in combination with dexamethasone for the frontline treatment of multiple myeloma

2009 ◽  
Vol 146 (6) ◽  
pp. 619-626 ◽  
Author(s):  
Sundar Jagannath ◽  
Brian G. M. Durie ◽  
Jeffrey Lee Wolf ◽  
Elber S. Camacho ◽  
David Irwin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Frontline Treatment

Updated Survival Analyses after Prolonged Follow-Up of the Phase 2, Multicenter CREST Study of Bortezomib in Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2717-2717 ◽  
Author(s):  
Sundar Jagannath ◽  
Bart Barlogie ◽  
James R. Berenson ◽  
David Siegel ◽  
D. Irwin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 2 ◽  
Initial Report ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Phase 2 Study ◽  
The Difference ◽  
Dose Levels ◽  
To Receive

Abstract Background: The initial report of the CREST phase 2 study (Br J Haematol2004;127:165–72) demonstrated the substantial activity of bortezomib (VELCADE®, Vc) at two different dose levels in patients with relapsed or refractory multiple myeloma (MM). Here, we provide an updated analysis of overall survival (OS) after prolonged follow-up (median >5 years). Methods: 54 patients were enrolled to receive Vc 1.0 mg/m2 (n=28) or 1.3 mg/m2 (n=26) on days 1, 4, 8, and 11 of a 21-day cycle, for up to 8 cycles. Dexamethasone (dex) 20 mg on the day of and day after each Vc dose was added for 16 (57%) patients in the 1.0 mg/m2 group and 12 (46%) patients in the 1.3 mg/m2 group, upon suboptimal response to Vc alone. A total of 17 (31%) patients continued to receive Vc ± dex in an extension study, 12 (43%) from the 1.0 mg/m2 and 5 (19%) from the 1.3 mg/m2 groups. Patients received a median of 3 (range, 1–7) prior regimens. Median time from diagnosis to first Vc dose was 2 years. In the 1.0 and 1.3 mg/m2 groups, respectively, mean age was 64 vs 60 years, 50% vs 35% of patients were male, 54% vs 65% had IgG MM, 58% vs 48% had β2-microglobulin ≥4 mg/L, and 29% vs 48% had abnormal cytogenetics. Response rate (CR+PR, EBMT criteria) to Vc alone was 30% vs 38%, and to Vc ± dex was 37% vs 50% in the 1.0 and 1.3 mg/m2 groups. OS from first dose of Vc in each dose group was analyzed using the Kaplan-Meier method. Results: Median OS in the 1.0 and 1.3 mg/m2 groups was 26.8 months and 60.0 months, after median follow-up of 61 and 65 months, respectively (Figure). In the 1.0 mg/m2 group, 21 (75%) patients have died; the 1- and 2-year OS rates were 82% and 54%, respectively. In the 1.3 mg/m2 group, only 14/26 (54%) patients have died; 1- and 2-year OS rates were 81% and 69%, respectively. Conclusions: Vc ± dex was active in relapsed or refractory MM at both the 1.0 mg/m2 and 1.3 mg/m2 dose levels and was associated with notable OS, particularly in patients treated with the approved Vc dose of 1.3 mg/m2. The difference in OS between dose groups suggests that the higher dose of Vc is more active. Figure. Kaplan-Meier analyses of OS in patients who received Vc 1.0 mg/m2 (n=28) or 1.3 mg/m2 (n=26). Figure Figure

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