Compassionate Use of Belantamab Mafodotin for Treatment of Patients with Relapsed/Refractory Multiple Myeloma Heavily Treated. Spanish Experience

Abstract Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.

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Expanded Access Program (EAP) for Lenalidomide (Revlimid®) Plus Dexamethasone in over 1400 Subjects with Relapsed or Refractory Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.3556.3556 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3556-3556 ◽

Cited By ~ 2

Author(s):

Christine Chen ◽

Donna E. Reece ◽

David Siegel ◽

Ruben Niesvizky ◽

Ralph Vincent Boccia ◽

...

Keyword(s):

Multiple Myeloma ◽

Phase Iii ◽

Advocacy Groups ◽

Refractory Multiple Myeloma ◽

Expanded Access ◽

Prior Therapy ◽

Expanded Access Program ◽

The Us ◽

Grade 3 ◽

Access Program

Abstract Background: Lenalidomide (Revlimid®) in combination with dexamethasone was approved in the US on June 29, 2006 for the treatment of subjects with multiple myeloma who had received at least one prior therapy. On February 28, 2005 based upon a positive interim analysis of two pivotal placebo-controlled Phase III studies, an independent Data Safety Monitoring Board recommended the studies be unblinded and all subjects in both studies be given access to lenalidomide. In April 2005, the FDA in association with myeloma patient advocacy groups requested Celgene establish an expanded access program to make lenalidomide plus dexamethasone available to subjects with relapsed or refractory multiple myeloma while the treatment was awaiting approval. Aim: To provide lenalidomide to multiple myeloma subjects with a high likelihood of benefit and to obtain additional safety data. Methods: Subjects with relapsed or refractory multiple myeloma that received at least 1 prior therapy were eligible. Subjects received 25 mg lenalidomide plus high-dose dexamethasone in 4-week cycles until disease progression was documented, study drug was discontinued, or lenalidomide became commercially available for this indication. Results: Between September 8, 2005 and July 25, 2006, approximately 1400 subjects in the US and Canada were enrolled into the study. A data snapshot taken March 17, 2006 demonstrated that 746 subjects had been enrolled, median age was 63 years, 60% were male, and 66.5% had Stage III disease. Median time on study was 7.1 weeks (0.1–24.4) and median daily dose was 20.5 mg. At least one Grade 3 or 4 adverse event was reported in 261 (35%) of the 746 subjects. Most commonly reported Grade 3–4 events were neutropenia (7.9% of subjects), thrombocytopenia (6.0%), fatigue (3.6%), anemia (3.5%), pneumonia (3.1%) and hyperglycemia (2.0%). These most commonly reported Grade 3–4 adverse events were the same as those found in the previous pivotal studies, however, their frequencies of occurrence were lower in the current study probably due to ongoing data collection and differences in study maturity. Likewise, the most commonly reported adverse events (all grades) were the same as those reported in the two previous pivotal studies. Conclusion: Preliminary data from this expanded access program in over 1400 subjects with multiple myeloma are consistent with results from two earlier Phase III pivotal studies. The EAP of lenalidomide plus dexamethasone in multiple myeloma represents a model of how government, advocacy groups, healthcare providers and industry can work together to quickly provide treatment to subjects in need while a clearly active treatment regimen is awaiting approval.

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Single agent vincristine by infusion in refractory multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.1985.3.11.1508 ◽

1985 ◽

Vol 3 (11) ◽

pp. 1508-1512 ◽

Cited By ~ 30

Author(s):

D V Jackson ◽

L D Case ◽

E K Pope ◽

D R White ◽

C L Spurr ◽

...

Keyword(s):

Multiple Myeloma ◽

Platelet Count ◽

Motor Function ◽

Single Agent ◽

Phase 2 ◽

Refractory Multiple Myeloma ◽

Phase 2 Trial ◽

Heavily Pretreated ◽

The Mean ◽

Wbc Count

A phase 2 trial of vincristine infusion was conducted in a group of 21 patients with refractory multiple myeloma. Patients were generally heavily pretreated with radiotherapy and chemotherapy. Vincristine was given intravenously (IV) as a 0.5 mg bolus and followed immediately by infusion of 0.25 to 0.50 mg/m2/d for 5 days. Courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Objective responses (partial) were noted in two patients (10%), both of whom were administered 0.5 mg/m2/d infusions. Response durations were brief (2.2 and 1.2 months). Toxicity consisted of neurotoxicity and myelosuppression. In addition to the occurrence of paresthesias and myalgias, ileus (two cases) and moderately severe loss of motor function (two cases) were observed. The mean lowest WBC count following treatment was 2.67 X 10(3)/microL v 3.96 X 10(3)/microL pretreatment (P = .008). The mean lowest platelet count was 75.0 X 10(3)/microL v 106.8 X 10(3)/microL pretreatment (P = .008). Vincristine infusion appears to have limited activity in the treatment of refractory multiple myeloma. Additionally, response durations were short lived and toxicity, both neurologic and hematologic, was appreciable.

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Pomalidomide (CC4047) Plus Low-Dose Dexamethasone (Pom/dex) Is Highly Effective Therapy in Relapsed Multiple Myeloma

Blood ◽

10.1182/blood.v112.11.866.866 ◽

2008 ◽

Vol 112 (11) ◽

pp. 866-866 ◽

Cited By ~ 4

Author(s):

Martha Q. Lacy ◽

Suzanne R. Hayman ◽

Morie A. Gertz ◽

Jacob B. Allred ◽

Sumithra J. Mandrekar ◽

...

Keyword(s):

Multiple Myeloma ◽

Low Dose ◽

Single Agent ◽

Objective Response ◽

Autologous Stem Cell Transplant ◽

Response To Therapy ◽

Cell Transplant ◽

Refractory Multiple Myeloma ◽

Prior Therapy ◽

Grade 3

Abstract Background: Thalidomide and its analogue lenalidomide have high response rates among patients with newly diagnosed as well as previously treated myeloma. Pomalidomide (CC4047) is the newest immunomodulatory (IMiD) agent that has shown single-agent activity in phase I studies. We report on the first Phase 2 trial of pomalidomide combined with low dose dexamethasone (Pom/dex) in patients with relapsed or refractory multiple myeloma. Methods: 37 patients (21 male and 16 female) were enrolled. Pomalidomide was given orally 2 mg daily on days 1–28 of a 28-day cycle. Dexamethasone was given orally at a dose of 40 mg daily on days 1, 8, 15 and 22 of each cycle. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily as prophylaxis against DVT. Results: The median age was 66 years (range, 40 – 88). All patients were evaluable for response and toxicity, and all analysis were done on intent to treat basis. All patients had received prior therapy; 38% had 3 prior regimens; 35% had 2 prior regimens and 27% had one prior regimen. 76% had previous autologous stem cell transplant (ASCT) and 24% had 2 prior ASCT. 62% had previous IMiD therapy. Toxicity was mild and consisted primarily of myelosuppression. Grade 3 neutropenia occurred in 31%; grade 3 thrombocytopenia 3%; grade 3 anemia 3 %. Other grade 3/4 toxicities seen in less than 5% pts included: diarrhea, atrial fibrillation, pneumonia, dehydration and renal insufficiency. 16 % had grade 1/2 neuropathy. No grade 3 neuropathy was seen and there have been no thromboembolic events. Thirty (81%) patients are continuing study treatment. Seven patients have discontinued treatment due to: disease progression (5), died on study (1) and the medical doctor’s discretion (1). Twenty three of 37 patients (62%) achieved an objective response to therapy; including 9 (24%) with VGPR; 14 patients (38%) with PR; 6 (16%) with stable disease. Objective responses were seen in 4 of 13 patients (29%) who were refractory to lenalidomide. Conclusions: Pomalidomide plus dexamethasone (Pom/dex) is highly active and well tolerated for treatment of relapsed/refractory multiple myeloma with an objective responserate of 62%, including a 29% response rate among patients who are lenalidomiderefractory.

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Phase I/II Study of Combination of Sorafenib, Vorinostat, and Bortezomib in Acute Myeloid Leukemia with FLT3-ITD Mutation or Monosomy 5, 7, or Complex Cytogenetics

Blood ◽

10.1182/blood.v124.21.976.976 ◽

2014 ◽

Vol 124 (21) ◽

pp. 976-976 ◽

Cited By ~ 1

Author(s):

Mohammad Abu Zaid ◽

H. Scott Boswell ◽

Larry D. Cripe ◽

Yan Liu ◽

Jill Weisenbach ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Conflicts Of Interest ◽

Hematologic Toxicity ◽

Refractory Disease ◽

Prior Therapy ◽

Poor Risk ◽

Common Grade ◽

Heavily Pretreated ◽

Ecog Ps

Abstract Introduction We report the phase I data from ongoing phase I/II study of combination of targeted agents sorafenib, vorinostat and bortezomib in poor-risk AML. Our findings from a previous phase I study, performed at Indiana University, of the combination of sorafenib and vorinostat in patients with AML suggested that two major groups of patients may benefit most from this targeted regimen, patients with FLT3-ITD mutation, and those with complex or poor-risk cytogenetics (monosomy 5 or 7). In addition, our findings were suggestive of a synergistic action obtained by inhibition of p52NFKB, a down-stream target of proteosome inhibition. With the hypothesis that addition of proteasome inhibitor bortezomib would be of benefit towards such synergism, a phase I/II clinical trial combining bortezomib with sorafenib and vorinostat was initiated. The phase I data is reported here. Methods The phase I portion of the trial utilized a traditional 3+3 design on five cohorts to determine the MTD of the combination. Eligibility required age ≥18, a confirmed baseline diagnosis of AML by the revised guidelines of the International Working Group for AML, and included untreated disease in elderly or relapsed/refractory disease in all ages, monosomy 5,7 or complex cytogenetics or positive FLT3-ITD mutation, ECOG PS 0-2, and adequate kidney and liver function. Dose limiting non-hematologic toxicity was defined per the CTCAE v4.0 criteria. Hematologic toxicity was prolonged cytopenia with <5% cellularity and no evidence of leukemia in the bone marrow lasting >42 days after discontinuation of therapy. The treatment was given in cycles, with each cycle consisting of 2 weeks treatment followed by 1 week off. Dose and/or administration schedule of drugs were escalated between the cohorts. Results Seventeen patients were enrolled on the phase I portion. Fifteen patients completed at least one cycle of treatment and 2 were taken off earlier due to disease progression. The median age was 51 years (24-73), and 10 (59%) patients were male. Sixteen patients had prior therapy at time of enrollment and 59% were heavily pretreated (≥3 lines of therapy) including stem cell transplantation in 29%. Fifty nine percent had FLT3-ITD mutation and 53% had poor-risk cytogenetics. No DLTs were seen in all 5 cohorts and MTD was not reached. The safe dose for phase II was determined at sorafenib 400 mg bid, vorinostat 200 mg bid (both for 14 days), and bortezomib 1.3 mg/m2IV on days 1,4,8,11, every 21 days. Most common grade 1-2 toxicities were diarrhea (59%), nausea (41%), vomiting (24%) and rash (18%). Majority of toxicities were grade 1. Response was observed in 6 patients (40%) with 4 achieving a complete remission (27%). All responders had relapse/refractory disease. Conclusion The combination of sorafenib, vorinostat, and bortezomib when given with a 2-week on, 1-week off schedule is safe with minimal side effects, and tolerable as an outpatient regimen for the treatment of poor-risk AML. Encouraging responses with this regimen are seen in these patients. The phase II portion of the study is currently ongoing. Correlative studies to further elucidate the molecular attributes of efficacy of this regimen in poor-risk AML are underway. Updated results will be presented. Disclosures No relevant conflicts of interest to declare.

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A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma

Leukemia ◽

10.1038/s41375-020-0857-2 ◽

2020 ◽

Vol 34 (12) ◽

pp. 3298-3309 ◽

Cited By ~ 4

Author(s):

Joseph Mikhael ◽

Joshua Richter ◽

Ravi Vij ◽

Craig Cole ◽

Jeffrey Zonder ◽

...

Keyword(s):

Multiple Myeloma ◽

Single Agent ◽

Proteasome Inhibitors ◽

Progression Free Survival ◽

Dose Finding ◽

Upper Respiratory Tract ◽

Phase 2 ◽

Refractory Multiple Myeloma ◽

Prior Therapy ◽

Tract Infections

AbstractA Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ≥3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38–85), 5 (2–14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses ≥10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade ≤2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade ≤2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses ≥10 mg/kg.

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Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma

Blood ◽

10.1182/blood-2008-12-196238 ◽

2009 ◽

Vol 114 (4) ◽

pp. 772-778 ◽

Cited By ~ 110

Author(s):

Paul Richardson ◽

Sundar Jagannath ◽

Mohamad Hussein ◽

James Berenson ◽

Seema Singhal ◽

...

Keyword(s):

Multiple Myeloma ◽

Single Agent ◽

Progression Free Survival ◽

Prior Treatment ◽

Once Daily ◽

Free Survival ◽

Refractory Multiple Myeloma ◽

Treatment Regimens ◽

Common Grade ◽

Grade 3

Abstract Lenalidomide plus dexamethasone is effective for the treatment of relapsed and refractory multiple myeloma (MM); however, toxicities from dexamethasone can be dose limiting. We evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed and refractory MM. Patients (N = 222) received lenalidomide 30 mg/day once daily (days 1-21 every 28 days) until disease progression or intolerance. Response, progression-free survival (PFS), overall survival (OS), time to progression (TTP), and safety were assessed. Overall, 67% of patients had received 3 or more prior treatment regimens. Partial response or better was reported in 26% of patients, with minimal response 18%. There was no difference between patients who had received 2 or fewer versus 3 or more prior treatment regimens (45% vs 44%, respectively). Median values for TTP, PFS, and OS were 5.2, 4.9, and 23.2 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which proved manageable with dose reduction. Grade 3 or 4 febrile neutropenia occurred in 4% of patients. Lenalidomide monotherapy is active in relapsed and refractory MM with acceptable toxicities. These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351.

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Phase I Study of 30-Minute Infusion of Carfilzomib As Single Agent or in Combination With Low-Dose Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.2013.52.3522 ◽

2015 ◽

Vol 33 (7) ◽

pp. 732-739 ◽

Cited By ~ 58

Author(s):

Kyriakos P. Papadopoulos ◽

David S. Siegel ◽

David H. Vesole ◽

Peter Lee ◽

Steven T. Rosen ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Concentration ◽

Phase I ◽

Phase I Study ◽

Low Dose ◽

Single Agent ◽

Phase Iii ◽

Maximum Plasma ◽

Irreversible Inhibitor ◽

Refractory Multiple Myeloma

Purpose Carfilzomib is an irreversible inhibitor of the constitutive proteasome and immunoproteasome. This phase I study evaluated the maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of carfilzomib administered as a 30-minute intravenous (IV) infusion. Safety and efficacy of carfilzomib as a single agent or in combination with low-dose dexamethasone were assessed. Patients and Methods Patients with relapsed and/or refractory multiple myeloma (MM) were administered single-agent carfilzomib on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Cycle one day 1 and 2 doses were 20 mg/m2, followed thereafter by dose escalation to 36, 45, 56, or 70 mg/m2. Additionally, carfilzomib was combined with low-dose dexamethasone (40 mg/wk). Results Thirty-three patients were treated with single-agent carfilzomib. Dose-limiting toxicities in two patients at 70 mg/m2 were renal tubular necrosis and proteinuria (both grade 3). The MTD was 56 mg/m2. Nausea (51.5%), fatigue (51.5%), pyrexia (42.4%), and dyspnea and thrombocytopenia (each 39.4%) were the most common treatment-related toxicities. Overall response rate (ORR) was 50% (56-mg/m2 cohort). Increasing carfilzomib dosing from 20 to 56 mg/m2 resulted in higher area under the plasma concentration-time curve from time zero to last sampling and maximum plasma concentration exposure with short half-life (range, 0.837 to 1.21 hours) and dose-dependent inhibition of proteasome chymotrypsin-like activity. In 22 patients treated with 45 or 56 mg/m2 of carfilzomib plus low-dose dexamethasone, the ORR was 55% with a safety profile comparable to that of single-agent carfilzomib. Conclusion Carfilzomib administered as a 30-minute IV infusion at 56 mg/m2 (as single agent or with low-dose dexamethasone) was generally well tolerated and highly active in patients with relapsed and/or refractory MM. These data have provided the basis for the phase III randomized, multicenter trial ENDEAVOR.

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Quantitative PK/PD Prediction of the Efficacious and Safe Dose Ranges of the LMP7 Inhibitor M3258 for Phase I Application in Relapsed/Refractory Multiple Myeloma Patients

Blood ◽

10.1182/blood-2019-126972 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5582-5582

Author(s):

Florian Lignet ◽

Christina Esdar ◽

Manja Friese-Hamim ◽

Andreas Becker ◽

Elise Drouin ◽

...

Keyword(s):

Multiple Myeloma ◽

Research And Development ◽

Phase I ◽

Dose Escalation ◽

Single Agent ◽

Proteasome Inhibitors ◽

Refractory Multiple Myeloma ◽

Oral Application ◽

Development Institute ◽

Safe Dose

M3258 is an orally bioavailable, potent, selective, reversible inhibitor of the large multifunctional peptidase 7 (LMP7, β5i, PSMB8) proteolytic subunit of the immunoproteasome; a crucial component of the cellular protein degradation machinery, which is highly expressed in malignant hematopoietic cells including multiple myeloma. M3258 was previously shown to deliver strong in vivo preclinical efficacy in multiple myeloma xenograft models, as well as a more benign non-clinical safety profile compared to approved pan-proteasome inhibitors, exemplified by a lack of effects on the central and peripheral nervous systems and cardiac and respiratory organs. Here we describe preclinical PK/PD and PK/efficacy modelling which led to a prediction of the PK profile, and the efficacious and safe dose ranges of M3258 in human which were used to guide the design of the phase I dose-escalation trial of M3258 in >3 line relapsed/refractory multiple myeloma (RRMM) patients. Mouse, rat, dog and monkey PK, plasma protein binding and intrinsic clearance data were used to estimate a half-life of approximately 6 hours for M3258 in human. The human total clearance and volume of distribution for M3258 were predicted to be 0.033 L/h/kg and 0.28 L/kg, respectively, whilst oral bioavailability was estimated to be above 80%. LMP7 proteolytic activity was assessed as a PD readout in human multiple myeloma tumor cells xenografted to mice as well as in dog peripheral blood mononuclear cells (PBMCs). A strong PK/PD relationship was observed for M3258 across both species. LMP7 inhibition by M3258 also correlated strongly with anti-tumor efficacy in multiple myeloma xenografts, with maximal efficacy observed at M3258 exposure delivering sustained inhibition of tumor LMP7 activity. Quantitative PK/PD/efficacy modeling predicted the biologically efficacious dose (BED) of M3258 upon oral application to be between 10 - 90 mg daily in human. By incorporating data from nonclinical safety studies, these data suggest an attractive human PK profile of M3258, enabling oral application, as well as an improved human therapeutic index compared to approved pan-proteasome inhibitors. M3258 is being investigated in a phase I, first-in-man, 2-part, open label clinical study designed to determine the safety, tolerability, PK, PD and early signs of efficacy of M3258 as a single agent (dose-escalation) and co-administered with dexamethasone (dose-expansion) in participants with RRMM whose disease has progressed following > 3 prior lines of therapy and for whom no effective standard therapy exists. Integration of these data will guide the selection of the BED for potential further clinical development of M3258. Disclosures Lignet: Merck Healthcare KGaA: Employment. Esdar:Merck Healthcare KGaA: Employment. Friese-Hamim:Merck Healthcare KGaA: Employment. Becker:Merck Healthcare KGaA: Employment, Other: Holding shares with a value below 1000-USD. Drouin:EMD Serono Research and Development Institute: Employment. El Bawab:Merck Healthcare KGaA: Employment. Goodstal:EMD Serono Research and Development Institute: Employment. Gimmi:Merck Healthcare KGaA: Employment. Haselmayer:Merck Healthcare KGaA: Employment. Jährling:Merck Healthcare KGaA: Employment. Sanderson:Merck Healthcare KGaA: Employment. Sloot:Merck Healthcare KGaA: Employment. Stinchi:Merck Healthcare KGaA: Employment. Victor:Merck Healthcare KGaA: Employment. Walter:Merck Healthcare KGaA: Employment. Rohdich:Merck Healthcare KGaA: Employment.

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An Experience on Pomalidomide in Patients within Relapsed/Refractory Multiple Myeloma - A Multicenter Study in Turkey

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2020/v32i4131047 ◽

2021 ◽

pp. 92-98

Author(s):

Mehmet Ali Erkurt ◽

Fehmi Hindilerden ◽

Omer Ekinci ◽

Jale Yildiz ◽

Mehmet Sinan Dal ◽

...

Keyword(s):

Multiple Myeloma ◽

Side Effects ◽

Cox Regression ◽

Single Agent ◽

Eastern Cooperative Oncology Group ◽

Cox Regression Analysis ◽

Refractory Multiple Myeloma ◽

Thalidomide Analogue ◽

New Generation

Objective: Pomalidomide is a new generation thalidomide analogue. Effectiveness as a single agent or combination with low dose dexamethasone has been in the treatment of relapse/refractory Multiple Myeloma (MM). The aim of the present study was to share the experience of different oncology centres with pomalidomide treatment in patients with relapsed/refractory MM. Materials and Methods: Seventy-three patients from 16 centres were enrolled into the study. The patients were followed for a median of 6 months. Relapsed/refractory MM patients who received at least one line of treatment before pomalidomide were included into the study. ISS, R-ISS and Eastern Cooperative Oncology Group (ECOG) scores of the patients and treatment-related side effects were evaluated. Results: As a result of the median follow-up for 6 months, 36% (26/72) of the patients presented progression. The estimated median PFS was found 29 months. The Cox regression analysis revealed that ECOG affected PFS only, myeloma subtype; ISS and R-ISS scores did not affect PFS. The most common side effects with pomalidomide treatment in our population include neutropenia, infections, anaemia and thrombocytopenia. Conclusion: In our study, it was statistically shown that the ECOG score was effective in survival in relapsed / refractory MM patients treated by pomalidomide. Therefore, we recommend evaluation of the ECOG score for each patient before treatment in eligible cases.

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