Realistic Lenalidomide Dose Adjustment Strategy for Transplant-Ineligible Elderly Patients with Relapsed/Refractory Multiple Myeloma: Japanese Real-World Experience

Lenalidomide is an immunomodulatory drug administered orally in the treatment of multiple myeloma. Some elderly patients require a reduced lenalidomide dose because of comorbidities and/or adverse events. This study investigated the actual dose of lenalidomide in elderly patients, finding that most received reduced (5-10 mg) doses. The most common reasons for dose reduction were renal dysfunction (54% of patients), fatigue (grade ≥3; 20%), hematologic disorder (grade ≥3; 14%), and rash (grade ≥3; 9%). Their median time to progression was 11.8 months and their median overall survival was 39.2 months. The overall response rate was 73%, including 17% with a complete response, 19% with a very good partial response, and 37% with a partial response. These results showed that, contrary to western countries, most patients were treated with a reduced dose of lenalidomide in Japan. However, it is suggested that continued treatment with a tolerable dose may yield favorable outcomes.

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

BioMed Research International ◽

10.1155/2014/145843 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 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.

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Autologous haematopoietic stem cell transplantation in patients with multiple myeloma complicated by dialysis-dependent renal failure

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.07.000777 ◽

2020 ◽

Vol 92 (7) ◽

pp. 70-76

Author(s):

M. V. Firsova ◽

L. P. Mendeleeva ◽

M. V. Solovev ◽

I. G. Rekhtina ◽

O. S. Pokrovskaya ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Stem Cell ◽

Partial Response ◽

Stem Cell Transplantation ◽

Haematopoietic Stem Cell Transplantation ◽

Complete Response ◽

Haematopoietic Stem Cell ◽

Renal Response ◽

Good Partial Response

Aim.To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure. Materials and methods.During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed. Results.The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%. Conclusion.Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.

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Prevalence of Oligoclonal Bands in Multiple Myeloma Patients Who Achieved Better Results Than Very Good Partial Response after Treatment with Standard or High Doses Chemotherapy-Final Analysis

Blood ◽

10.1182/blood.v126.23.4210.4210 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4210-4210

Author(s):

Luiza soares Vieira ◽

Edvan de queiroz Crusoe ◽

Manuella de S. Sampaio Almeida ◽

Lais Sousa ◽

ana Lucia Perez ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Conflicts Of Interest ◽

Progression Free Survival ◽

Final Analysis ◽

Complete Response ◽

High Dose Chemotherapy ◽

Oligoclonal Bands ◽

High Dose ◽

Good Partial Response

Abstract Introduction - Oligoclonal bands (OB) are monoclonal proteins distinct from those originally identified in the multiple myeloma (MM) diagnosis. Some authors consider that appearance of these bands confers a better prognosis and may be linked to immune reconstitution. There is no data of the exact prevalence of OB emergence in patients with very good partial response (VGPR) or better after different treatment schedules. Objectives - To determine the prevalence of OB in MM patients treated with or without high-dose chemotherapy that obtained at least VGPR and its prognostic value. Methods- This is a retrospective and prospective cohort study. Data were collected from records of patients that achieved at least VGPR to identify the OB emergence. Subsequently, new sample collections from the positive patients were made in order to monitor the progress and duration of the maintenance of these bands. Results-Median follow-up was 42m and 101 patients were included. Median age was 58y (29-87) and 55% were male. IgG was the most frequent component (60%). Durie-Salmon IIIA/B was identified in 92% of the population; ISS was 33% in stage I, 30% in stage II, and 31% in stage III. The prevalence of OB identified by SPE and IF was 50.5% (51 cases), with a higher prevalence in those who underwent transplantation and those who achieved complete response (p=0.00139 and p=0.0368, respectively). Progression free survival (PFS) was longer in the OB group (45.4m x 34.7m p = 0.0075). Conclusion - The OB prevalence in this population was 50.5% and oligoclonality resulted in a longer PFS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials

Frontiers in Pharmacology ◽

10.3389/fphar.2021.758992 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yali Tao ◽

Hui Zhou ◽

Ting Niu

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Adverse Events ◽

Response Rate ◽

Complete Response Rate ◽

Meta Analysis ◽

Complete Response ◽

Cochrane Central Register ◽

Safety And Efficacy ◽

Grade 3

Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma.Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX).Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18–67%), 55% (32–78%), 5% (−2–13%), 7% (4–11%), 14% (5–24%), 23% (15–31%), 11% (8–14%), 26% (14–38%) and 14% (4–23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p < 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p < 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p < 0.00001), nausea (72 vs 52%, p < 0.00001), vomiting (41 vs 23%, p < 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p < 0.0001) than SEL + DEX treatment in grade≥3 AEs.Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.

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Combination Therapy Based on Bortezomib for Newly Diagnosed Multiple Myeloma Patients

Blood ◽

10.1182/blood.v120.21.5048.5048 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5048-5048

Author(s):

Jingsong He ◽

Li Yang ◽

Dian Jin ◽

Xuanru Lin ◽

Qianqian Yang ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Combination Therapy ◽

Conflicts Of Interest ◽

Complete Response ◽

Chinese Patients ◽

Newly Diagnosed ◽

Serious Adverse Events ◽

Novel Drugs ◽

Grade 3

Abstract Abstract 5048 Introduction: Novel drugs, such as bortezomib, have significantly improved the response rates in multiple myeloma (MM), but little has been reported on bortezomib-based therapies in Chinese patients. Methods: In the initial eight 28-day cycles, newly diagnosed ymptomatic patients were treated with combination therapy including bortezomib plus dexamethasone (PD) and the triplet combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), thalidomide (PDT) between February 1, 2006 and May 31, 2012. Among the above regimens, bortezomib (1. 3 mg/m2) was given intravenously on days 1, 4, 8, 11, while dexamethasone (20 mg/m2/day) was given intravenously on days 1–2, 4–5, 8–9, 11–12, adriamycin (10 mg/m2) was given intravenously on days 1–4, cyclophosphamide (200 mg/m2) was given intravenously on days 1–4 and thalidomide (100 mg) was administered orally each day. Results: The overall response rate (¡Ý partial response, PR) of all the 151 eligible patients was 88. 7% (including 29. 8% very good partial response (VGPR) and 25. 8% complete response/near complete response (CR/nCR). The responses per IMWG criteria for patients are shown in Table 2. The median PFS was 20. 3 months (95% CI: 14. 8–25. 8 months) in the patients who received PDT, 24. 8 months (95% CI: 20. 0–30. 0 months) in the patients who received PCD, 22. 9 months (95% CI: 17. 6–28. 2 months) in patients who received PAD and 21. 8 months (95% CI: 15. 3–28. 3 months) in the patients who received PD with no significant differences between the groups. The median OS for PD arm was 42. 0(95% CI: 20. 1–63. 9 months) months while other arms were not reached, but the median OS for PDT, PCD and PAD was significant longer than PD (P=0. 042, 0. 039, 0. 010). PFS and OS for patients with favorable cytogenetics were significantly longer than those with unfavorable cytogenetics by FISH. The frequently observed hematologic toxicities (Grade 3/4) were: thrombocytopenia (17. 00%), neutropenia (15. 00%) and anemia (8. 61%). The most common non-hematologic toxicities included (all Grades) peripheral neuropathy(57. 61%), fatigue(27. 15%), infection(23. 84%), constipation(22. 52%), herpes zoster(17. 22%) and diarrhea(15. 23%). Conclusions: Our experience indicated that bortezomib-based regimens were active and well-tolerated for MM patients, and triplet combinations were superior to PD. Serious Adverse events were rare in the Chinese patients with MM who received bortezomib-based chemotherapy. Disclosures: No relevant conflicts of interest to declare.

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Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): An open-label, phase 1b study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8000 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8000-8000 ◽

Cited By ~ 21

Author(s):

Andrzej J. Jakubowiak ◽

Ajai Chari ◽

Sagar Lonial ◽

Brendan M. Weiss ◽

Raymond L. Comenzo ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Safety Profile ◽

Standard Of Care ◽

Complete Response ◽

Newly Diagnosed ◽

Open Label ◽

Frontline Treatment ◽

Grade 3

8000 Background: DARA in combination with established standard of care regimens prolongs PFS, deepens responses, and demonstrates a favorable safety profile in relapsed or refractory multiple myeloma (MM). The tolerability and efficacy of DARA-KRd in newly diagnosed MM pts was examined. Methods: Newly diagnosed pts regardless of transplantation eligibility were enrolled. Pts received DARA 16 mg/kg QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter. All pts received the 1st dose of DARA split over 2 days. Carfilzomib (K) was administered on Days 1, 8 and 15 of each 28-day cycle (20 mg/m2 on C1D1, 36 or 70 mg/m2 subsequently based on tolerability of first dose) for ≤13 cycles or elective discontinuation for ASCT. Lenalidomide 25 mg was given on Days 1-21 and dexamethasone 20-40 mg per week. The primary endpoint was tolerability. Results: Twenty-two pts (median [range] age, 60 [34-74] y) were enrolled and received a median of 8 (1-10) treatment cycles. Nineteen pts escalated K dose to 70 mg/m2 by C1D15. Median (range) duration of follow-up was 7.4 (4.0-9.3) months. Six (27%) pts discontinued treatment (1 AE [pulmonary embolism]; 1 PD; 4 other [ASCT]). Serious AEs occurred in 46% of pts, and 14% were possibly related to DARA; 18 (82%) experienced a grade 3/4 TEAE. The most common grade 3/4 TEAEs (>10%) were lymphopenia (50%) and neutropenia (23%); 1 (5%) cardiac grade 3 TEAE was observed (congestive heart failure) which resolved; pt quickly resumed study treatment with reduced K dose. No grade 5 TEAE was reported. All DARA-associated infusion reactions (27% of pts) were grade ≤2. Treatment with DARA-KRd yielded an ORR (≥partial response) of 100% (5% complete response, 86% ≥very good partial response) in 21 response-evaluable pts. The 6-month PFS rate was 100%. Conclusions: The addition of DARA to KRd was well tolerated; the overall safety profile was consistent with that previously reported for KRd, with no additional toxicity observed with the addition of DARA. Deep and durable responses were observed. These data support further investigation of DARA-KRd as a frontline treatment regimen. Updated data will be presented based on longer follow up. Clinical trial information: NCT01998971.

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Pomalidomide (CC4047) Plus Low-Dose Dexamethasone As Therapy for Relapsed Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.2009.23.6802 ◽

2009 ◽

Vol 27 (30) ◽

pp. 5008-5014 ◽

Cited By ~ 225

Author(s):

Martha Q. Lacy ◽

Suzanne R. Hayman ◽

Morie A. Gertz ◽

Angela Dispenzieri ◽

Francis Buadi ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Partial Response ◽

Low Dose ◽

Progression Free Survival ◽

Complete Response ◽

Hematologic Toxicity ◽

High Risk Disease ◽

Grade 3

Purpose Thalidomide and lenalidomide are immunomodulatory drugs (IMiDs) that produce high remission rates in the treatment of multiple myeloma. Pomalidomide is a new IMiD with high in vitro potency. We report, to our knowledge, the first phase II trial of pomalidomide administered in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma. Patients and Methods Pomalidomide was administered orally at a dose of 2 mg daily on days 1 through 28 of a 28-day cycle. Dexamethasone 40 mg daily was administered orally on days 1, 8, 15, and 22 of each cycle. Responses were recorded using the criteria of the International Myeloma Working Group. Results Sixty patients were enrolled. Thirty-eight patients (63%) achieved confirmed response including complete response in three patients (5%), very good partial response in 17 patients (28%), and partial response in 18 patients (30%). Responses were seen in 40% of lenalidomide-refractory patients, 37% of thalidomide-refractory patients, and 60% of bortezomib-refractory patients. Responses were seen in 74% of patients with high-risk cytogenetic or molecular markers. Toxicity consisted primarily of myelosuppression. Grade 3 or 4 hematologic toxicity consisted of anemia (5%), thrombocytopenia (3%), and neutropenia (32%). One patient (1.6%) had a thromboembolic event. The median progression-free survival time was 11.6 months and was not significantly different in patients with high-risk disease compared with patients with standard-risk disease. Conclusion The combination of pomalidomide and low-dose dexamethasone is extremely active in the treatment of relapsed multiple myeloma, including high response rates in patients refractory to other novel agents.

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Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia

Blood ◽

10.1182/blood-2011-03-339077 ◽

2011 ◽

Vol 118 (13) ◽

pp. 3489-3498 ◽

Cited By ~ 128

Author(s):

Xavier C. Badoux ◽

Michael J. Keating ◽

Sijin Wen ◽

Bang-Ning Lee ◽

Mariela Sivina ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Partial Response ◽

Elderly Patients ◽

Progression Free Survival ◽

Complete Response ◽

Initial Therapy ◽

Lymphocytic Leukemia ◽

Common Grade ◽

Grade 3

Abstract The best initial therapy for elderly patients with chronic lymphocytic leukemia (CLL) has not yet been defined. We investigated the activity of lenalidomide as initial therapy for elderly patients with CLL. Sixty patients with CLL 65 years of age and older received treatment with lenalidomide orally 5 mg daily for 56 days, then titrated up to 25 mg/d as tolerated. Treatment was continued until disease progression. At a median follow-up of 29 months, 53 patients (88%) are alive and 32 patients (53%) remain on therapy. Estimated 2-year progression-free survival is 60%. The overall response rate to lenalidomide therapy is 65%, including 10% complete response, 5% complete response with residual cytopenia, 7% nodular partial response, and 43% partial response. Neutropenia is the most common grade 3 or 4 treatment-related toxicity observed in 34% of treatment cycles. Major infections or neutropenic fever occurred in 13% of patients. Compared with baseline levels, we noted an increase in serum immunoglobulin levels across all classes, and a reduction in CCL3 and CCL4 plasma levels was noted in responding patients. Lenalidomide therapy was well tolerated and induced durable remissions in this population of elderly, symptomatic patients with CLL. This study was registered at www.clinicaltrials.gov as #NCT00535873.

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28-Day Metronomic Therapy for Relapsed Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2020-142210 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 13-13

Author(s):

Tarek H Mouhieddine ◽

Julia Hieulle ◽

Erin Moshier ◽

Josh R. Richter ◽

Hearn Jay Cho ◽

...

Keyword(s):

Clinical Trial ◽

Multiple Myeloma ◽

High Risk ◽

Partial Response ◽

Clinical Benefit ◽

Research Funding ◽

Complete Response ◽

Chemotherapeutic Agents ◽

Metronomic Therapy ◽

Grade 3

Background: The advent of novel therapies has led to tremendous progress in the treatment of multiple myeloma (MM). However, management of patients with high-risk disease who have failed approved agents and have rapidly progressive disease with cytopenias continues to be challenging. While palliative care is an option, many patients hope to qualify for a clinical trial option. Here we report results of a 28-day metronomic therapy (METRO-28) consisting of continuous administration of very low doses of classical chemotherapeutic agents. Sixteen-day cycles of metronomic therapy were previously shown to have a favorable response with acceptable toxicity profiles in MM patients (Papanikolaou et al. Haematologica 2013). Aim: To investigate the efficacy and toxicity in patients with high-risk relapsed refractory MM (RRMM) ineligible for clinical trial options receiving 1 cycle of METRO-28. Method: We retrospectively analyzed the clinical outcomes of 106 RRMM, treated with 1 cycle of 28-day metronomic chemotherapy at the Tisch Cancer Institute - The Mount Sinai Hospital. METRO-28 consists of 6 agents: dexamethasone 8 mg on days 1 through 4, 7 through 10, 13 through 16, 19 through 22 and 25 through 28; bortezomib 1 mg/m2 on days 1, 4, 7, 10, 13, 16, 19, 22, 25, 28; cisplatin 1 mg/m2 daily; doxorubicin 1 mg/m2 daily; thalidomide 100 mg daily; and vincristine flat dose 0.06 mg daily. METRO-28 was administered through a central line in either the inpatient or outpatient setting. Result: Our cohort of 106 RRMM patients has a median age of 65 years (range: 35-85) and at a median of 59 months from time of diagnosis; 42% were females. They had a median of 7 prior lines of therapy (range: 1 - 25); with 73% triple- and 58% penta-refractory cases. Prior autologous transplantation was utilized in 69% of patients including tandem transplants in 30%. Moreover, 78% of patients carried high-risk cytogenetic features, including 1q21 duplication/amplification (89%), 17p deletion (49%), t(4;14) (17%), t(14;16) (17%) or t(14;20) (3%). At the time of METRO-28 initiation, patients were cytopenic with grade 3 and 4 anemia (21%), neutropenia (8%) and thrombocytopenia (23%). Profound cytopenias in some patients led to early discontinuation of treatment; forty-three patients (41%) received the full 28-day course of METRO-28, while 11%, 17%, 20% and 11% were treated for <1 week, <2 weeks, <3 weeks or <4 weeks, respectively. Grade 3-4 cytopenia increased: anemia 66%, leucopenia 61%, neutropenia 55% and thrombocytopenia 76%. On an intent to treat basis (106 patients), the deepest response included 2% stringent complete response (sCR), 7% near complete response (nCR), 7% very good partial response (VGPR), 28% partial response (PR), 11% minimal response (MR) and 12% stable disease (SD). Only 43 patients (41%) completed all 4 weeks of METRO-28 and had a 72% overall response rate (ORR) and 88% clinical benefit rate (CBR). Seventy-four percent of these patients were able to move on to new therapies, including novel agents and clinical trials. Their overall survival (OS) was 11.8 months (range: 6.1-NE) as opposed to an OS of 4.2 months (range: 3.4-7.2) for patients with <4 weeks of METRO-28. Sixty-three patients had their treatment interrupted: 34 due to disease progression or absence of response, 18 due to bacterial or viral infections and 11 due to hematologic toxicity. Conclusion: Giving 1 cycle of METRO-28 is better tolerated in patients with good hematologic reserve and offers an opportunity for a clinical benefit and a bridge to a subsequent treatment option for these advanced refractory myeloma patients. Disclosures Richter: Takeda: Consultancy; Janssen: Speakers Bureau; Sanofi: Consultancy; AstraZeneca: Consultancy; X4 Pharmaceuticals: Consultancy; Adaptive Biotechnologies: Consultancy, Speakers Bureau; Oncopeptides: Consultancy; Secura Bio: Consultancy; Antengene: Consultancy; Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy, Speakers Bureau. Parekh:Foundation Medicine: Consultancy; Celgene: Research Funding; Karyopharm: Research Funding. Chari:Adaptive Biotechnology: Honoraria; The Binding Site: Honoraria; Array BioPharma: Honoraria; Novartis: Honoraria; Secura Bio: Consultancy; Glaxo Smith Kline: Consultancy; Antengene: Consultancy; Takeda: Consultancy, Research Funding; Oncopeptides: Consultancy; Seattle Genetics: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Research Funding; Bristol Myers Squibb: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Jagannath:Legend Biotech: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Madduri:Janssen: Consultancy; BMS: Consultancy; Takeda: Consultancy; Legend: Consultancy; Sanofi: Consultancy; GSK: Consultancy; Kinevant: Consultancy; Foundation Medicine: Consultancy.

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Thalidomide Response in African American Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.5147.5147 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5147-5147

Author(s):

Ahmad Jajeh ◽

Rose Catchatourian ◽

Deimante Tamkus ◽

David Osafo ◽

Ghassan Zalzaleh ◽

...

Keyword(s):

Multiple Myeloma ◽

African American ◽

Partial Response ◽

Light Chain ◽

Complete Response ◽

Total Response Rate ◽

Back Ground ◽

One Year ◽

Beta 2 Microglobulin ◽

Good Partial Response

Abstract African american are not well presented in clinical trials. This is a retrospective analysis studying Thalidomide response in predominantly african american patients with multiple myeloma from January 2000 till August 2005. A total of fifty patients diagnosed with multiple myeloma started on Thalidomide which was given through the S.T.E.P. Program. Twenty one males and twenty nine females. Thirty six african americans (72%), eleven hispanics (22%), three whites and one other. Mean age at starting treatment is 63 years (range 41–76). All were stage II-III. Mean serum Albumin is 3.4mg/dL (range 2.2–4.7) and Beta 2 microglobulin is 3.8 (range 0.60–13.6), the normal range is 0–0.63 mg/dL. Twenty four patients with IgG kappa, twelve patients with IgG lambda, three with lambda light chain, three with kappa light chain, seven patients with IgA and one patient with non secretory MM. Mean Thalidomide dose is 100 mg Oraly, daily (range 50–200 mg). Medium duration of therapy is one year (range 3 months- three and a half years). Two patients stopped in the first few weeks because of intolerance due to side effects. Eighty percent of patients given treatment after failure to prior therapies. Fifty percent of patients recieved Thalidomide with Dexamethason. Response were evaluated as of Blade criterae. Seven patients (14%) achieved complete response CR or very good partial response. Partial response PR was achieved in nine patients (18%), minimal response was achieved in three patients (6%) and stable disease in six (12%). Total response rate of fifty percent(50%). Fifteen patients (30%) achieved a rise in back ground depressed serum level of IgA (range 1–3 folds of normal value). Two patients(4%) achieved arise in the back ground depressed level of IgG in IgA MM. Median time to progression in patients with CR and PR was not reached. However most of the progression occured at one and a half years from response. Conclusion: Thalidomide alone or in combination with Dexamethasone is a well tolerated regimen. Low dose as 50 to 100mg seem to be effective and tolerated in most of the african american patients. The rise in IgA level is an interesting phenomena. This is particularly seen in CR and very good partial response. Whether this is an immune response or an epiphenomena need to be investigated.

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