T-Bird (thalidomide, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], Dexamethasone) Therapy for Upfront Use in Symptomatic Multiple Myeloma.

Abstract Abstract 1861 Poster Board I-886 Background: BiRD therapy (clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) for use as upfront therapy in symptomatic multiple myeloma in 72 patients yielded impressive results: over 90% achieved at least a partial response (PR), with nearly 40% in complete response (CR). We hypothesized that we could safely increase the immunomodulatory benefit of the BiRD combination with the addition of low-dose thalidomide to the regimen, since these drugs have non-overlapping toxicities. A trial of T-BiRD (thalidomide, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) therapy for use in up-front treatment of symptomatic multiple myeloma (MM) was initiated to test safety and efficacy. Methods: Eighteen patients were enrolled in a single-institution trial of T-BiRD therapy for symptomatic MM. The T-BiRD regimen consists of clarithromycin 500mg twice daily, dexamethasone on days 1,8,15,22 of a 28-day cycle, and lenalidomide 25mg for days 1–21 of a 28-day cycle. Thalidomide is given at a dose of 50mg daily for the first week and thereafter at 100mg daily. Thromboprophylaxis with aspirin (162 mg once weekly, 81mg on subsequent days) was used for all subjects. Serum protein electrophoresis/immunofixation as well as free light chain determinations were done monthly. Bone marrow biopsy and either skeletal imaging were done at to confirm disease progression or CR. This protocol continues to accrue with a planned enrollment of 25 patients. Results: The median number of T-BiRD cycles was 5.5 (range 1–6). Twelve patients (67%) had achieved at least a partial response (PR) by cycle 1, compared to a median response time of 2 cycles for BiRD. Mean percent drop in M-protein for evaluable patients at each cycle is as follows: Cycle 1 – 61%, Cycle 2 – 77%, Cycle 3 – 79%, Cycle 4 – 81%, Cycle 5 – 93%, Cycle 6 – 92%. For 9 subjects who received 5 cycles of therapy, the overall response rate was 100%, with all but one subject achieving a VGPR or better. On an intent to treat basis, the VGPR or better rate was 55% because of patient withdrawal due to toxicity. A total of 10 subjects (56%) experienced an adverse event (AE), some study-drug related (RAE) during treatment. Seven subjects (39%) withdrew from the study due to drug toxicity: 2 had grade 2 skin rash prior to initiation of full-dose thalidomide (RAE), 1 patient had grade 4 skin rash (Stevens-Johnsons syndrome, SJS) during cycle 1 of T-BiRD (RAE), 1 had a TIA in cycle 2, 1 developed renal failure in cycle 1, 1 developed chest pain in cycle 3. Other toxicities include 1 patient with Grade 2 steroid myopathy (RAE), 1 patient with DVT of the leg (RAE), and 1 patient with atrial fibrillation. 1 subject died of progressive myeloma prior to completion of 1 cycle. Conclusions: T-BiRD is a highly effective first-line regimen for rapid and profound treatment response of multiple myeloma. Toxicity from T-BiRD may preclude its long-term use since many of the enrolled patients experienced an adverse event. Disclosures: Mark: Celgene: Research Funding, Speakers Bureau. Zafar:Celgene Corp: Speakers Bureau; Millenium: Speakers Bureau. Crann:Milllennium: Membership on an entity's Board of Directors or advisory committees. Niesvizky:Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding, Speakers Bureau; Proteolix: Consultancy, Research Funding.

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ClaPD (Clarithromycin/[Biaxin®], Pomalidomide, Dexamethasone) Therapy in Relapsed or Refractory Multiple Myeloma

Blood ◽

10.1182/blood.v118.21.635.635 ◽

2011 ◽

Vol 118 (21) ◽

pp. 635-635 ◽

Cited By ~ 2

Author(s):

Tomer M Mark ◽

Melissa Rodriguez ◽

Manan Shah ◽

Ryann Quinn ◽

Jessica Campbell ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Disease Progression ◽

Board Of Directors ◽

Research Funding ◽

Response Rate ◽

Complete Response ◽

Phase 2 ◽

Advisory Committees ◽

Dexamethasone Therapy

Abstract Abstract 635 Background: The addition of clarithromycin has been reported to enhance anti-myeloma activity of lenalidomide+dexamethasone in the upfront treatment of multiple myeloma (MM). Pomalidomide is a distinct IMiD® immunomodulatory agent with a significant response rate in subjects with relapsed or refractory MM (RRMM), including those with prior lenalidomide treatment. We hypothesized that clarithromycin may similarly enhance the activity of pomalidomide + dexamethasone in patients with RRMM after prior lenalidomide therapy. We now report the initial results from a phase 2 trial of ClaPD (Clarithromycin/[Biaxin®], Pomalidomide, Dexamethasone) therapy in RRMM. Methods: Fifty-two patients with heavily pre-treated RRMM were enrolled into a single-institution study and received ClaPD. Eligible subjects had at least 3 prior lines therapy, one line of which must have included lenalidomide. ClaPD is clarithromycin 500mg twice daily; dexamethasone 40mg on days 1,8,15,22; and pomalidomide 4mg for days 1–21 of a 28-day cycle. All subjects had thromboprophylaxis with aspirin. Disease response evaluation was performed monthly with immunoelectrophoresis and free light chain analysis; bone marrow biopsy with skeletal imaging was used to confirm MM progression or complete response (CR). Treatment was continued as tolerated by the patient until disease progression. Results: Forty-six patients had completed at least 1 cycle of ClaPD and were eligible for analysis. The median number of cycles received was 6 (range 2–10). ClaPD responses were progressive disease (PD): 20%, stable disease (SD): 15%, minimal response (MR): 7%, partial response (PR): 33%, very good partial response (VGPR): 20%, stringent complete remission (sCR): 7%, giving an overall response rate (ORR) of 60% and a ≥VGPR rate of 27%. In responding patients, time to PR was rapid at a median of 1.5 cycles (range 1–7). After a median follow up time of 6.7 months, 28 patients (61%) remain on study free from disease progression and 39 patients (85%) are alive. Two patients withdrew from treatment due to regimen toxicity (one due to Grade 3 fatigue, another due to Grade 4 muscular weakness). Conclusions: ClaPD is a highly effective regimen for heavily treated RRMM, particularly in patients with disease progression after prior lenalidomide therapy. When compared to other published Phase 2 data, the addition of clarithromycin in ClaPD appears to enhance the efficacy of Pomalidomide-Dexamethasone in lenalidomide-relapsed patients, (ORR 60% versus 40% - Lacy et. al JCO 2009) without induction of excess toxicity. Response to ClaPD is rapid, well tolerated, and sustained at > 6 months in the majority of subjects. These data support the use of pomalidomide therapy in RRMM that has progressed after lenalidomide. Disclosures: Mark: Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: There is no FDA indication for pomalidomide at this time. Zafar:Celgene Corp: Speakers Bureau. Pekle:Celgene Corp: Speakers Bureau. Coleman:Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Niesvizky:Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Research Funding.

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Sequence Impact Of Pomalidomide and Carfilzomib On Treatment Response In Relapsed Multiple Myeloma

Blood ◽

10.1182/blood.v122.21.1954.1954 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1954-1954 ◽

Cited By ~ 1

Author(s):

Tomer M Mark ◽

John N. Allan ◽

Angelique Boyer ◽

Adriana C Rossi ◽

Roger N Pearse ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Board Of Directors ◽

Research Funding ◽

Complete Response ◽

Salvage Chemotherapy ◽

Advisory Committees ◽

Effective Response ◽

Disease Response ◽

Prior Therapy

Abstract Background Pomalidomide and Carfilzomib (Cfz) are two recently approved agents for the treatment of multiple myeloma (MM) that has relapsed after prior therapy including an IMiD and bortezomib. The sequencing of these agents to achieve maximum tumor reduction is thus far not known. We have previously reported response data from the combination clarithromycin, pomalidomide, dexamethasone (ClaPD) for relapsed or refractory MM. (Mark et al, ASH 2012). We examined the subset of these patients that had received a Cfz-based regimen prior to ClaPD as well as the subset of patients that received a Cfz-based regimen after ClaPD to determine whether the sequence of agents had any impact on response. Methods One hundred nineteen patients with heavily pretreated RRMM were enrolled into a single-institution study to investigate the effectiveness and tolerability of ClaPD. Eligible subjects had at least 3 prior lines of therapy, one line of which must have included lenalidomide. ClaPD is clarithromycin 500mg twice daily; pomalidomide 4mg for days 1-21, and dexamethasone 40mg on days 1,8,15,22 of a 28-day cycle. Two subsets of patients were compared: 1) Subjects that had received treatment with a Cfz-based prior to ClaPD (CP) and 2) Subjects that had received a Cfz-based therapy after progression on ClaPD (PC). Disease response evaluation was performed monthly with immunoelectrophoresis and free light chain analysis; bone marrow biopsy with skeletal imaging was used to confirm MM progression or complete response (CR). Results Fourteen patients comprised CP and 20 in PC. Patients in the CP group were more heavily pre-treated with a median of 6 (range 3-15) lines of therapy, as compared to 5 lines (range 3-10) for PC. Responses are shown in Table 1. Median cycles of ClaPD and Cfz received in PC was 6.5 (range 2-16) and 5 (1-14), respectively. Median cycles of Cfz and ClaPD in the CP group was 8 (1-19) and 5 (1-23), respectively. CR complete response; VGPR: very good partial response; PR: partial response; SD: stable disease; PD: progressive disease; ORR: overall response rate Conclusions ClaPD and a Cfz-based regimen appear to have equally effective response regardless of sequence in salvage chemotherapy. Somewhat deeper responses are seen with ClaPD after Cfz as compared to Cfz after ClaPD, which is intriguing given that the CP group had more prior lines of treatment than PC. Longer follow-up to analyze duration of the response is needed prior to concluding which sequence (PC vs CP) is more effective. This data supports the use of pomalidomide after carfilzomib failure and vice-versa as potent salvage therapeutic options. Disclosures: Mark: Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Rossi:Celgene: Speakers Bureau. Zafar:Celgene: Speakers Bureau; Millennium: Speakers Bureau; Onyx: Speakers Bureau. Pekle:Celgene: Speakers Bureau; Millennium: Speakers Bureau. Niesvizky:Millennium: The Takeda Oncology Company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Real-World Clinical Outcomes By Cytogenetic Risk Category in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in France

Blood ◽

10.1182/blood.v128.22.4784.4784 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4784-4784

Author(s):

Huamao Mark Lin ◽

Keith L Davis ◽

James A. Kaye ◽

Katarina Luptakova ◽

Lu Gao ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Partial Response ◽

Research Funding ◽

Complete Response ◽

Line Treatment ◽

Second Line ◽

High Risk Patients ◽

Risk Patients ◽

Standard Risk

Abstract INTRODUCTION: Multiple Myeloma (MM) is an incurable hematologic cancer characterized by multiple recurrences. With each recurrence, patients have a lower probability of response and duration of response is shorter. Therefore, there is an unmet need to improve outcomes in relapsed/refractory multiple myeloma (RRMM). There is a shortage of data describing clinical features and outcomes in these patients in real-world practice, particularly with regard to differences in outcomes by baseline cytogenetic risk. To help address this information gap, this study analyzed data from a cohort of RRMM patients in France. METHODS: A retrospective observational review of medical records was conducted in a cohort of 200 patients with RRMM in France. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 40 hematology/oncology providers across France practicing mainly in academic hospitals. Inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) first-line (induction) regimen of chemotherapy with or without stem cell transplant (SCT) and with or without other post-induction/SCT therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients could be alive or deceased at the time of record abstraction. Baseline cytogenetic risk was defined as follows: high-risk: cytogenetic abnormalities del(17p), t(4:14), or t(14;16); unknown/unassessed risk: patients for whom cytogenetics were unavailable; or standard-risk: all patients with known cytogenetics not classified as high-risk. Patients were assessed for treatment response, overall survival (OS) and progression-free survival (PFS) from date of first relapse (study index date). All analyses were descriptive. Survival was assessed using the Kaplan-Meier (K-M) method. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. A total of 55 high-risk and 113 standard-risk patients were identified; risk category was unknown or unassessed for 32 patients. Among all patients, mean (SD) age at RRMM diagnosis was 66.3 (8.9) years and 62% of the sample was male. Lenalidomide + dexamethasone was the most common second-line systemic regimen initiated (50% of high-risk patients, 59.5% of standard-risk patients receiving second-line treatment). A total of 114 patients (57%) initiated a third-line treatment. Despite clinical response in second-line treatment occurring sooner in high-risk patients (median: 106 days) than in standard-risk patients (median: 237 days), physician-assessed overall response rate (ORR) was lower in high-risk patients (63%: 17% complete response, 46% partial response) than standard-risk patients (91%: 26% complete response, 65% partial response) across all second-line treatments combined (Table 2).. For third-line treatment, ORR was lower in high-risk patients (54%: 12% complete response, 42% partial response) than standard-risk patients (74%: 9% complete response, 65% partial response). Among patients who initiated a second-line treatment (n = 192), 47.4% were deceased at the time of data collection. From second-line initiation, K-M estimates of 1- to 5-year OS and PFS were substantially lower for high-risk patients versus standard-risk. Specifically, the proportions of patients still alive 1, 3, and 5 years after second-line treatment initiation were 73%, 51%, and 36%, respectively, for high-risk patients and 94%, 73%, and 61% for standard-risk patients. The proportions of patients without disease progression at 1, 3, and 5 years after second-line initiation were 48%, 13.5%, and 5% for high-risk patients and 82%, 42%, and 14% for standard-risk patients. CONCLUSIONS: The importance of cytogenetic risk classification as a prognostic factor in RRMM was apparent in this retrospective review, in which patients with high-risk cytogenetics had less favorable outcomes in terms of ORR, OS, and PFS than standard-risk patients. Decreased response rate and lower PFS and OS was documented among patients with high-risk cytogenetics, which is in contrast to shorter time needed to achieve best clinical response in this subgroup. Results from this real-world study provide further confirmation of the unmet medical need presented by RRMM, especially for patients with high-risk cytogenetics. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Gao:Takeda: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

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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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Updated Report of T-Bird (thalidomide, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], Dexamethasone) Therapy for Upfront Use In Symptomatic Multiple Myeloma

Blood ◽

10.1182/blood.v116.21.3050.3050 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3050-3050

Author(s):

Tomer M Mark ◽

Jennifer O'Loughlin ◽

Morton Coleman ◽

David Jayabalan ◽

Roger N Pearse ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Skin Rash ◽

Complete Response ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy ◽

Dexamethasone Therapy

Abstract Abstract 3050 Background: We hypothesized that the addition of thalidomide to BiRD therapy (clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) may improve the anti-myeloma activity of the combination while not adding to overall regimen toxicity, given the different side effect profiles of thalidomide and lenalidomide. We now report an update of the phase 2 trial of T-BiRD (thalidomide/Thalomid®, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) therapy for use in up-front treatment of symptomatic multiple myeloma (MM). Methods: Twenty-six patients with newly-diagnosed symptomatic MM were enrolled in a single-institution trial of T-BiRD. The T-BiRD regimen consists of clarithromycin 500mg twice daily, dexamethasone 40mg on days 1,8,15,22 of a 28-day cycle, and lenalidomide 25mg for days 1–21 of a 28-day cycle. Thalidomide is given at a dose of 50mg daily for the first week and thereafter at 100mg daily. All subjects had thromboprophylaxis with aspirin, 162 mg once weekly, 81mg on subsequent days throughout all treatment. Serum protein electrophoresis/immunofixation as well as free light chain determinations were done monthly. Bone marrow biopsy and skeletal imaging were done to confirm disease progression or complete response (CR). Results: Twenty-five patients had completed at least one cycle of T-BiRD and were evaluable. The median number of T-BiRD cycles was 5 (range 1–12). Response to T-BiRD, audited at time of autologous stem cell transplantation (ASCT) or other planned change in therapy, was: 1 (4%) progression of disease (PD), 4 (16%) stable disease (SD), 10 (40%) partial response (PR), 8 (32%) very good PR (VGPR), 1 (4%) complete response (CR), and 1 (4%) with unconfirmed CR, giving a overall response rate (ORR; 3PR) of 80% and a 3VGPR rate of 40%. Nine subjects subsequently underwent ASCT as part of a first line of therapy with T-BiRD induction. These subjects had an ORR of 100% to first-line therapy, with 2 maintaining PR (22%) 5 achieving VGPR (56%), and 2 achieving CR (22%). At three years of follow-up, median progression free survival (PFS) and event free survival (EFS) was not reached for first line therapy (median PFS and EFS censoring at time of ASCT were 65 and 53 weeks, respectively). Median overall survival (OS) was not reached; at 3-year follow-up, 2 patients had died of progressive myeloma, giving an overall survival rate of 92%. A total of 12 subjects (48%) experienced an adverse event (AE), 5 (20%) being study-drug related (RAE). Eight subjects (32%) withdrew from the study: 2 had grade 2 skin rash prior to initiation of full-dose thalidomide (RAE), 1 patient had grade 4 skin rash (Stevens-Johnsons syndrome, SJS) during cycle 1 (RAE), 1 had a TIA in cycle 2, 1 developed renal failure in cycle 1, 1 developed chest pain in cycle 3. Other toxicities include 1 patient with Grade 2 steroid myopathy (RAE), 1 patient with DVT of the leg (RAE), and 1 patient with atrial fibrillation. 2 subjects developed pneumonia (causitive organism not identified). 1 subject died of progressive myeloma prior to completion of 1 cycle. Conclusions: T-BiRD has promising activity as an induction regimen as part of first-line therapy for MM, with prolonged responses; however, toxicity limited extended use. T-BiRD does not appear to be superior to BiRD in ORR, likely due to shorter average time of regimen exposure (median 5 cycles of T-BiRD versus 13 cycles of BiRD). These data continue to support the role of lenalidomide-based regimens in the upfront treatment of MM. Disclosures: Mark: Celgene Corp: Speakers Bureau. Off Label Use: Lenalidomide - upfront use in myeloma. Coleman:Celgene Corp: Speakers Bureau. Zafar:Celgene Corp: Speakers Bureau. Leonard:BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Niesvizky:Celgene Corp: Consultancy, Speakers Bureau.

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The Efficacy of Salvage Autologous Stem Cell Transplant for Patients with Multiple Myeloma Who Received Maintenance Therapy Following Initial Transplant

Blood ◽

10.1182/blood.v128.22.3563.3563 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3563-3563 ◽

Cited By ~ 2

Author(s):

Justin A King ◽

Mark A Fiala ◽

Daniel R Kohnen ◽

Tanya M Wildes ◽

Keith Stockerl-Goldstein ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Maintenance Therapy ◽

Research Funding ◽

Overall Response Rate ◽

Response Rate ◽

Complete Response Rate ◽

Complete Response ◽

Median Number ◽

Overall Response

Abstract Background: For patients relapsing after initial autologous stem cell transplantation (ASCT), a second ASCT is a potential, although infrequently used, salvage option. Until recently, the benefits of second ASCT were unclear but recent prospective studies have shown second ASCT to improve PFS and OS compared to conventional salvage therapy. However, these studies have included few patients who received maintenance therapy following initial ASCT as maintenance therapy is a relatively recent innovation and is not standard of care in many EU countries where these studies where these studies were completed. Therefore, it is not currently clear if these patients benefit similarly from second ASCT. Methods: We performed retrospective chart review of patients with multiple myeloma that received two ASCTs, one for initial treatment and one for salvage at time of relapse, between 2008 and 2016 at our institution. We identified 30 who received maintenance therapy following initial therapy; 2 patients were excluded as they experienced treatment related mortality prior to disease assessment post-ASCT, leaving 28 for the analysis. Results: The median age of the study population was 59 years (range 48-69) at second ASCT. 64% (n = 18) were males, 36% (n = 10) females. Prior to initial ASCT, the median number of induction cycles was 4 (range 2-11). 86% (n = 24) of patients received bortezomib during induction, 39% (n = 11) lenalidomide, 7% (n = 2) cyclophosphamide, and 11% (n = 3) received another agent. All patients received melphalan conditioning for initial ASCT. Maintenance therapy consisted mostly of lenalidomide (93%, n = 26); 7% (n = 2) had bortezomib maintenance due to lenalidomide intolerance. The overall response rate (ORR) was 100% (n = 28); the complete response rate was 39% (n =11). The median progression-free survival (PFS) post-ASCT was 31 months (range 9-57), the median interval between initial and salvage ASCT was 38 months (range 22-63). At relapse, 93% (n =26) received reinduction chemotherapy while 7% (n = 2) went directly to salvage ASCT. The median number of reinduction cycles was 4 (range 2-28). 54% (n = 15) of patients received carfilzomib during reinduction, 46% (n = 13) bortezomib, 32% (n = 9) cyclophosphamide, 29% (n = 8) lenalidomide, 14% (n = 4) pomalidomide, and 7% (n = 2) received another agent. Prior to second ASCT, 79% (n =22) received melphalan conditioning, while 21% (n = 6) received BEAM. 79% (n = 22) received maintenance therapy post transplantation; 39% (n = 11) received bortezomib, 21% (n = 6) pomalidomide, 11% (n = 3) lenalidomide, 7% (n =2) carfilzomib, 18% (n = 5) were observed off maintenance, and 4% (n = 1) had frank progression post-ASCT prior to starting maintenance. The overall response rate (partial response or better) was 86% (n = 24); the complete response rate was 21% (n = 6). The median estimated PFS was 12 months (95% CI 10-15). The median duration of follow-up was 16 months; the estimated 2 year overall survival was 49%. Conclusion: In patients who relapse post-ASCT with maintenance therapy, the PFS following salvage ASCT is ~40% that of the initial ASCT. Strategies to improve outcomes using novel reinduction, conditioning, and post-transplant maintenance regimens are needed for these patients. Table Table. Disclosures Wildes: Carevive Systems: Consultancy. Vij:Shire: Consultancy; Jazz: Consultancy; Karyopharma: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding.

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Comparison of Minimal Residual Disease Detection between the Manual and Automated Gating Strategies of Euroflow Next-Generation Flow in Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2019-122398 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3083-3083

Author(s):

Hiroyuki Takamatsu ◽

Takeshi Yoroidaka ◽

Takeshi Yamashita ◽

Ryoichi Murata ◽

Mikio Ueda ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Pharmaceutical Company ◽

Research Funding ◽

Plasma Cells ◽

Residual Disease ◽

Next Generation ◽

Chugai Pharmaceutical ◽

Company Limited ◽

Minimal Residual

Background: The rate of complete response (CR) in multiple myeloma (MM) has dramatically increased because of the development of novel agents. In addition, the development of methods for measuring minimal residual disease (MRD), such as multiparameter flow cytometry and next-generation sequencing, has made it possible to stratify CR patients according to the MRD extent. EuroFlow next-generation flow (EuroFlow-NGF) is considered one of the gold standard methods for evaluating the negative status of MRD in MM. The automated gating strategy of EuroFlow-NGF has been shown to detect MRD as accurately as the manual gating strategy by experts. Oberle et al. (Haematologica, 2017) have found that daratumumab persisted on the surface of myeloma cells treated with it and that the anti-CD38 multi-epitope antibody used in EuroFlow-NGF has partial cross-reactivity with daratumumab, leading to generally lower mean fluorescence intensities of CD38. Therefore, MRD levels may have been underestimated in patients who were treated with anti-CD38 monoclonal antibodies (mAbs) using the automated gating strategy, leading to inappropriate management of the patients. Because no studies have examined the correlation of MRD extent between the manual and automated gating strategies in patients with MM who have received anti-CD38 mAbs, we compared MRD detection between the two gating strategies of EuroFlow-NGF in patients with MM. Methods: The study included bone marrow samples from 51 patients with MM (27 male and 24 female patients), including 13 patients treated with anti-CD38 mAb (12 treated with daratumumab and 1 treated with isatuximab). The median patient age was 70 years (range, 32-92 years) at MRD assessment. The disease statuses at MRD assessment were stringent CR in 26 patients (51%), CR in 7 (14%), very good partial response in 13 (26%), partial response in 1 (2%), and progressive disease in 4 (8%). The sample preparation protocol, Ab panel, and automated gating strategy of EuroFlow-NGF have been reported previously (Flores-Montero et al. Leukemia 2017). Briefly, we performed the EuroFlow-NGF method, which involved ammonium chloride-based bulk lysis, followed by surface staining using antibodies against CD138-BV421, CD27-BV510, CD38 multiepitope (ME)-FITC, CD56-PE, CD45-PerCP Cy5.5, CD19-PECy7, CD117-APC, and CD81-APC C750 in tube 1 and surface/intracellular staining using antibodies against CD138-BV421, CD27-BV510, CD38 ME-FITC, CD56-PE, CD45-PerCP Cy5.5, CD19-PECy7, CD117-APC, CD81-APC C750, cytoplasmic (cy) Igκ-APC, and cyIgλ-APC C750 after permeabilization in tube 2. For data analysis, events from both eight-color tubes (tubes 1 and 2) were merged, and the values of all parameters per tube were mathematically calculated using the merge and calculation functions of Infinicyt software (Cytognos SL, Salamanca, Spain). Automatic identification and enumeration of total plasma cells (tPCs) and abnormal plasma cells (MRD) were performed using the automatic gating function of Infinicyt software as described previously (Flores-Montero et al. Leukemia 2017). We compared the total nucleated cell number, tPC ratio, and MRD ratio between the manual (by experts) and automated gating strategies of EuroFlow-NGF. Results: In patients with MM who did not receive any anti-CD38 mAb therapy, we observed high correlations for both the tPC (r = 0.959, P < 0.0001) (Figure A) and MRD (r = 0.974, P < 0.0001) (Figure B) ratios between the manual and automated gating strategies of EuroFlow-NGF. On the other hand, in patients with MM who received anti-CD38 mAb therapy, we did not observe good correlations for both the tPC (r = 0.349, P = 0.2) (Figure A) and MRD (r = 0.292, P = 0.3) (Figure B) ratios between the two strategies owing to a lower fluorescence intensity of CD38 on PCs. In addition, when the MRD threshold was set to 10-5, the discordance of MRD positivity/negativity between the two strategies was significantly higher in patients who received anti-CD38 mAb therapy than in those who did not receive anti-CD38 mAb therapy [4/13 (31%) vs. 1/38 (3%), P = 0.012]. Conclusion: Although the automated gating strategy of EuroFlow-NGF could be a viable alternative to the manual strategy for the assessment of MRD in MM, we may have to utilize the manual strategy to obtain precise MRD results for patients with MM who received anti-CD38 mAbs. Figure Disclosures Takamatsu: Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Ono pharmaceutical: Honoraria, Research Funding; CSL Behring: Research Funding; SRL: Consultancy, Research Funding; Janssen Pharmaceutical: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Fujimoto Pharmaceutical: Honoraria; Becton, Dickinson and Company: Honoraria; Abbvie: Consultancy; Daiichi-Sankyo Company: Honoraria. Yoroidaka:Ono Pharmaceutical: Honoraria. Yamashita:Janssen Pharmaceutical K.K.: Honoraria; Daiichi-Sankyo Company: Honoraria; Kyowa Kirin: Honoraria; Chugai Pharmaceutical Co.,Ltd: Honoraria; TEIJIN PHARMA LIMITED: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Bristol-Myers Squibb: Honoraria; Ono Pharmaceutical: Honoraria; Celgene: Honoraria. Murata:Celgene: Honoraria; Ono pharmaceutical: Honoraria. Nakao:Daiichi-Sankyo Company, Limited: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; SynBio Pharmaceuticals: Consultancy; Ohtsuka Pharmaceutical: Honoraria; Celgene: Honoraria; Ono Pharmaceutical: Honoraria; Novartis Pharma K.K: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Chugai Pharmaceutical Co.,Ltd: Honoraria; Kyowa Kirin: Honoraria; Alaxion Pharmaceuticals: Honoraria. Matsue:Novartis Pharma K.K: Honoraria; Ono Pharmaceutical: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Celgene: Honoraria; Janssen Pharmaceutical K.K.: Honoraria.

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Daratumumab, Pomalidomide, and Dexamethasone (DPd) for the Treatment of Relapsed/Refractory Multiple Myeloma: A Single Institution Experience

Blood ◽

10.1182/blood-2018-99-117497 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5642-5642 ◽

Cited By ~ 1

Author(s):

Al-Ola Abdallah ◽

Neil Dunavin ◽

Brian McClune ◽

Leyla Shune ◽

Ajoy L. Dias ◽

...

Keyword(s):

Multiple Myeloma ◽

Proteasome Inhibitor ◽

Research Funding ◽

Median Number ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Duration Of Treatment ◽

Effective Treatment Option ◽

Refractory Multiple Myeloma ◽

Overall Response

Abstract Background: Daratumumab triplet regimens containing dexamethasone and lenalidomide or bortezomib are an effective treatment option for patients with relapsed/refractory multiple myeloma (RRMM). Daratumumab was recently FDA-approved in combination with the second-generation immunomodulatory drug, pomalidomide, and dexamethasone based (DPd) on results of the EQUULEUS study where overall response rates (ORR) of 60% were seen. The goal of this retrospective study was to analyze clinical outcomes of the DPd triplet regimen in either a daratumumab and pomalidomide naïve or refractory population of heavily pretreated RRMM patients at our institution. Methods: Thirty-two patients with RRMM treated with DPd at the University of Kansas Health System between November 2015 and July 2018 were included in our analysis. DPd consisted of 28-day cycles of daratumumab 16 mg/kg intravenously (weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, and every 4 weeks thereafter until disease progression); pomalidomide 4 mg orally (PO)on Days 1-21 and adjusted for cytopenia or toxicities; and dexamethasone 40 mg PO weekly adjusted based on tolerance. based on age. Responses were evaluated using IMWG criteria. Patient characteristics, disease course, and outcomes were summarized with descriptive statistics. Kaplan-Meier analyses were used to estimate progression-free (PFS) and overall survival (OS). Results:The median age was 64 years (range 44-83). Twenty-three patients (72%) had IgG isotype, 11 patients (34 %) had ISS stage III disease at diagnosis, 13 patients (41%) had high risk cytogenetics, and 13 patients (41%) had extramedullary disease. Median number of previous lines of therapy was 4 (1-9). Twenty-two patients (69%) received ≥3 prior therapies. Twenty-three patients (72%) were proteasome inhibitor refractory, 28 patients (88%) were immunomodulator refractory, 9 patients (28%) were daratumumab refractory, and 3 patients (15%) were double refractory to daratumumab and pomalidomide. Twenty-eight patients (88%) had received autologous stem cell transplant (ASCT) prior to DPd; 12 patients (38%) had ≥2 prior transplants. Median number of DPd cycles received was 6 (2-30) and the median duration of treatment was 5 months (2-30). At a median follow-up of 8.4 months (range: 2-29), the overall response rate (ORR) for all patients was 72% which compares favorably to the ORR of 60% in the EQUULEUS study. However, about half of the responses were partial responses (PR) (47%). The ORR rate for those who were refractory to either pomalidomide or daratumumab was 65%. The PFS was 8.3 months, while the median OS was not reached. Conclusion: DPd was recently approved for the treatment of RRMM. Our ORR compares favorably to the EQUULEUS study, however about half of responses were partial responses or better. Surprisingly, our analysis shows an impressive ORR in patients with previous exposure to proteasome inhibitor and immunomodulatory therapies in RRMM population, suggesting a benefit of DPd even in patients who received prior pomalidomide or daratumumab. Disclosures McGuirk: Astellas Pharma: Research Funding; Gamida Cell: Research Funding; Novartis Pharmaceuticals Corporation: Honoraria, Other: speaker, Research Funding; Pluristem Ltd: Research Funding; Kite Pharma: Honoraria, Other: travel accommodations, expenses, speaker ; Fresenius Biotech: Research Funding; Bellicum Pharmaceuticals: Research Funding. Ganguly:Daiichi Sankyo: Research Funding; Janssen: Consultancy; Amgen: Consultancy; Seattle Genetics: Speakers Bureau.

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A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma

Blood ◽

10.1182/blood-2020-141243 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 29-29

Author(s):

Walter Hanel ◽

Beth A. Christian ◽

Kami J. Maddocks ◽

Narendranath Epperla ◽

Basem M. William ◽

...

Keyword(s):

Board Of Directors ◽

Median Time ◽

Research Funding ◽

Response Rate ◽

Immune Escape ◽

Chronic Gvhd ◽

Complete Response ◽

Median Number ◽

Hodgkin's Lymphoma ◽

Advisory Committees

Introduction: Classical Hodgkin's Lymphoma (cHL) is characterized by an extensive inflammatory infiltrate with abundant Th2 and Treg cells which facilitate immune escape of Reed Sternberg (RS) cells and provides a growth promoting microenvironment by cytokine secretion and CD40/CD40L engagement. Our group previously show that ibrutinib irreversibly inhibits both Bruton's tyrosine kinase (BTK) and interleukin-2 inducible kinase (ITK), a kinase important in Th2 signaling (Dubovsky et al Blood 2013). We hypothesized that the addition of ibrutinib to nivolumab would lead to deeper and more durable responses in cHL by normalizing the Th1/Th2 balance thus reversing immune escape of RS cells. We present results of a planned interim analysis of the first 10 patients enrolled with a data cutoff of June of 2020. Methods: This is a single arm, phase II, single institutional clinical trial testing the clinical activity of nivolumab in combination with ibrutinib in patients ≥18 years of age with histologically confirmed cHL who have received at least one prior line of therapy and who were either not candidates for or had a prior autologous stem cell transplant (ASCT). Prior treatment with nivolumab was allowed. Ibrutinib was administered at 560 mg daily until progression in combination with nivolumab 3 mg/kg IV every 3 weeks for 16 cycles. The primary objective was complete response rate (CRR) prior to cycle 7 assessed per Lugano criteria. Adverse events (AEs) were reported using CTCAE Version 4.0. Results: Of the first 11 cHL patients enrolled, one patient withdrew consent prior to initiating therapy. Of the remaining 10 patients, the median age was 41 years (range 20-84) and 4 patients (40%) were male. The median number of prior lines of treatment was 4.5 (range 1-11), 5 patients (50%) had prior ASCT, 8 patients (80%) had prior brentuximab, and 5 patients (50%) had prior nivolumab. Four of the five patients with prior nivolumab had progressed while receiving therapy while the remaining patient had stable disease upon completing nivolumab with a median time from the last nivolumab treatment of 15.6 months (range 0.7-23.2). Of the 10 patients who received treatment, one patient came off study after two cycles due to persistent grade 2 transaminitis lasting for several weeks attributed to nivolumab requiring high dose oral steroids. One patient came off study after cycle 9 due to grade 3 hematuria attributed to ibrutinib and another came off study due to a pericardial effusion after 8 cycles of ibrutinib maintenance. In the remaining patients, treatment was generally well tolerated with most AEs being grade 1-2 (Table 1). The median number of total cycles received was 9 (range 2-22). Of the 9 patients evaluable for response, 6 patients responded (ORR = 66%), 4 of whom had a complete response (CRR = 44%) with a median time to response of 2 months (Table 2, Fig.1). In intention-to-treat analysis, the ORR was 60% and CRR was 40% meeting our prespecified interim efficacy endpoint of a 30% CRR for trial continuation. Notably, of the 5 patients with prior nivolumab, 3 responded to nivolumab + ibrutinib (ORR = 60%), with one having a CR (CRR = 20%). Overall, at a median follow up of 9.5 months, both the median PFS and duration of response have not yet been reached, with 3 patients remaining in CR at the time of data cutoff. Three of 4 patients discontinued trial treatment to undergo SCT [2 allogeneic; 1 autologous]. Of the 2 allogeneic SCT patients, the first one underwent SCT 3 weeks after the last nivolumab infusion and developed multi-organ acute graft-versus-host disease (GVHD) followed by severe chronic GVHD requiring extracorporeal photopheresis. The second patient underwent allogeneic SCT 2 months following the last nivolumab infusion and had no acute GVHD and experienced only mild chronic GVHD which was medically managed. Conclusions: Although the numbers are small and further recruitment is ongoing (target n=17), the combination of ibrutinib and nivolumab was generally well tolerated and with high response rate with more than half of responding patients achieving a CR. In addition, responses were seen in patients with prior nivolumab treatment. Our results suggest a possible novel role for BTK inhibition in reversing nivolumab resistance in cHL, at least in some cases. Correlative studies including peripheral blood and tumor immune subset analyses are ongoing and the latest results will be presented at the meeting. Disclosures Christian: Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Maddocks:Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. William:Incyte: Research Funding; Dova: Research Funding; Celgene: Consultancy, Honoraria; Seattle Genetics: Research Funding; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Guidepoint Global: Consultancy. Jaglowski:Novartis: Consultancy, Research Funding; CRISPR: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy. Bond:Seattle Genetics: Honoraria. Brammer:Celgene Corporation: Research Funding; Seattle Genetics, Inc.: Speakers Bureau. Baiocchi:viracta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Consultancy, Research Funding. OffLabel Disclosure: This trial uses ibrutnib in cHL to augment the responses of concurrent nivolumab administration.

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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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