Multiple Myeloma In Japan Research Articles

Evaluation of the Effectiveness of Additional Risk Minimization Measures for Ixazomib Citrate for Relapsed/Refractory Multiple Myeloma in Japan: A Web-Based Survey Among Pharmacists.

Ixazomib citrate (IXA) in combination with lenalidomide and dexamethasone (IRD therapy) has been approved for the treatment of relapsed or refractory multiple myeloma. In Japan, as these three drugs have different dosing schedules, dosing instructions for patients have been prepared and distributed to patients via healthcare professionals to promote an understanding of the appropriate dosing regimen, as an additional risk minimization measure (aRMM). This survey aimed to investigate whether the aRMM material is being utilized for the adequate use of IXA. A web-based questionnaire survey was conducted among in-hospital pharmacists in Japan who instructed patients on IXA dosing for IRD therapy. The primary endpoint was the proportion of pharmacists who provided patients with the contents of the aRMM material (i.e., how to take IXA). The secondary endpoints were the proportion of pharmacists who had obtained the aRMM material and the proportion of pharmacists who understood the importance of explaining how to take IXA to patients. Of the 330 pharmacists who completed the questionnaire, 93.0% answered that they had explained how to take IXA to patients. Of those who answered that they had explained how to take IXA, 33.2% responded that they had experience in using the aRMM material. In addition, 37.6% of the pharmacists answered that they had obtained the aRMM material. Moreover, 95.8% stated that they knew how to take IXA, and 90.3, 9.1, 0.3, and 0.3% of pharmacists answered that the importance of explaining how to take IXA was "very important," "probably important," "less important" and "not important," respectively. How to take IXA was explained to patients by pharmacists and the aRMM material was utilized at the time of the explanation, indicating that the aRMM material contributes to the promotion of the appropriate use of IXA.

An observational study of once-weekly carfilzomib in patients with multiple myeloma in Japan (Weekly-CAR study).

Background: The ARROW study demonstrated that once-weekly carfilzomib and dexamethasone (wKd) therapy significantly prolonged progression-free survivalcompared with twice-weekly carfilzomib and dexamethasonetherapy in relapsed or refractory multiple myelomapatients. Aim: To describe the treatment patterns, effectiveness and safety of wKd therapy in real-world settings in Japan. Methods: We investigated data from the medical records of 126 Japanese patients with relapsed or refractory multiple myeloma. Results: The overall response rate was 66.3%. The median progression-free survival was 9.5months. The incidence of treatment-emergent adverse events of any grade and grade ≥3 were 45.8and 20.8%, respectively. Conclusion: There were no new or unexpected safety signals in this study. This study demonstrated the effectiveness and safety profiles of wKd therapy in Japan.

A prospective, multicenter, observational study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in Japan

Real-world studies permit inclusion of a more diverse patient population and provide more information on the effectiveness of treatments used in routine clinical practice. This prospective, multicenter, observational study investigated the effectiveness and safety of ixazomib plus lenalidomide and dexamethasone (IRd) in 295 patients with relapsed/refractory multiple myeloma (RRMM) in routine clinical practice in Japan. Patients had a median age of 74 years, 80.0% were aged ≥ 65 years, 42.0% had received ≥ 3 lines of prior treatment, and 28.5% were “frail” according to the International Myeloma Working Group frailty score. After a median follow-up of 25.0 months, median progression-free survival (PFS) was 15.3 (95% CI 12.4–19.5) months, while median overall survival was not reached. The overall response rate was 53.9%, and 31.5% of patients had a very good partial response or better. In the subgroup analysis, median PFS was better in patients with 1 versus 2 or ≥ 3 lines of prior treatment (29.0 vs 19.2 or 6.9 months) and paraprotein versus clinical relapse (16.0 vs 7.9 months), but median PFS was not notably affected by frailty score or age group. Dose adjustment was more frequent among patients aged > 75 years, especially early after IRd treatment initiation. Treatment-emergent adverse events (TEAEs) of any grade occurred in 84.4% of patients and 24.7% of patients discontinued treatment due to TEAEs; no new safety concerns were found. These findings suggest that oral IRd triplet regimen is an effective and tolerable treatment option for RRMM patients in real-world settings outside of clinical trials.ClinicalTrials.gov identifier: NCT03433001; Date of registration: 14 February 2018.

II. Current Treatment Strategies for Multiple Myeloma in Japan

II. Current Treatment Strategies for Multiple Myeloma in Japan

Treatment pattern and clinical outcomes in multiple myeloma patients in Japan using the Medical Data Vision claims database.

Multiple myeloma therapy has made remarkable progress with the advent of new drugs. We explored the treatment pattern and outcomes in Japanese patients with multiple myeloma using the Medical Data Vision database. Patients were categorized as per the initial diagnosis period (2003-2015 and 2016-2020), considering the adoption of these new agents and then based on stem cell transplantation. Overall, 6438 patient data were extracted as eligible for data analysis, and the median age at the index diagnosis date was 72.0 years. Bortezomib/dexamethasone was the most common regimen for induction therapy in patients requiring stem cell transplantation from 2003-2015, and the use of bortezomib/lenalidomide/dexamethasone increased from 2016-2020. Lenalidomide/dexamethasone was the most commonly used post-transplant therapy. In the non-stem cell transplantation group, bortezomib/dexamethasone was mainly used for both periods, while lenalidomide/dexamethasone was primarily used from 2016-2020. There was a trend toward shorter first-line treatment duration and a shift to additional treatment patterns with new drugs at the following lines. The time to inpatient death period suggested an improvement between the two periods. Thus, this study revealed that recent diversification of treatment options is preferred and contributes to improved outcomes in the clinical practice of multiple myeloma in Japan.

Evaluating process utilities for the treatment burden of chemotherapy in multiple myeloma in Japan: a time trade-off valuation study

AimsThis study estimated the “process utilities” of treatment options for patients with relapsed/refractory multiple myeloma (RRMM) in Japan using the time trade-off (TTO) method. Chimeric antigen receptor (CAR) T cell immunotherapy is available for patients with RRMM who are triple-class exposed (TCE) after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies. However, the impact of available treatment options on health state utilities has not been well characterized, particularly in relation to process utilities.MethodsEight vignettes of health states and daily activity restrictions related to each of the following RRMM therapies were prepared: no treatment, CAR T cell therapy with idecabtagene vicleucel (ide-cel), regular intravenous infusion, and oral administration. A face-to-face survey of healthy Japanese adults who were representative of the general population was conducted. The TTO method was used to evaluate each vignette and to generate utility scores for each treatment regimen.ResultsThree hundred and nineteen respondents participated in the survey (mean age: 44 years [range: 20–64]; female: 50%). Utility scores for no treatment, ide-cel, oral pomalidomide, and dexamethasone (Pd) therapy ranged from ∼0.7 to 0.8. Utility scores for regular intravenous infusion regimens ranged from 0.50 to 0.56. There was a difference of ∼0.2 between the utility scores for no treatment/ide-cel/oral administration and regular intravenous infusions.ConclusionsDifferences in treatment administration across RRMM therapies showed a substantial impact on health state utilities. When quantifying the value of treatments, process utility gains should be considered as an independent factor in health technology assessments.

Practice patterns and outcomes for triple-class exposed patients with relapsed/refractory multiple myeloma in Japan.

Aim: Treatment options for triple-class exposed (TCE) patients with multiple myeloma (MM) in Japan are limited. Materials & methods: Retrospective observational study using the Medical Data Vision database (April 2008-April 2021). Eligible adults with MM received a new post-TCE treatment. Treatments, healthcare resource utilization (HCRU)and costs (per patient per month [PPPM]) were analyzed with subgroup analyses by prior stem cell transplantation (SCT vs No SCT). Results: Of 459 TCE patients, 216 (47%) had post-TCE treatment of whom 194 (90%) had no prior SCT. Median duration of the first post-TCE line of therapy (LOT) was 2months; 49% of No SCT patients received a subsequent LOT. Total healthcare costs were comparable between No SCT and SCT groups (¥1.3million PPPM each; US$12,328 and $12,391, respectively), driven by treatment costs. Median post-index overall survival(n=216) was 15.8months (95% CI: 10.5, 22.3). Conclusion: New treatments with better effectiveness are needed for patients with TCE MM in Japan.

Recent advances in the management of older adults with newly diagnosed multiple myeloma in Japan.

Multiple myeloma is a cancer of plasma cells; the incidence rate of multiple myeloma is high among older adults. Although significant advances have been made in the clinical management of multiple myeloma driven by the introduction of novel drugs, such as proteasome inhibitors, immuno- modulators and antibodies, multiple myeloma remains incurable. Hence, the current therapeutic goal for multiple myeloma is to achieve long-term survival while maintaining a good quality of life. In this context, personalized treatment to balance the efficacy and safety of therapies is important, especially for older adults as they display diverse physical, cognitive or organ functioning. Furthermore, old age is also often associated with frailty. Several tools for evaluating frailty in older adults with multiple myeloma are now available, and frail patients defined by these tools have shown a poor prognosis and more treatment-related toxicities. In addition, it is important to evaluate other factors, such as the International Staging System, high-risk chromosomal abnormalities and treatment response, to predict the clinical course of patients. Further investigations are required to determine how these factors can optimize the treatment for multiple myeloma. In this review, we present a detailed account on the developments and issues related to the current treatment approaches for older adults with newly diagnosed multiple myeloma. We also discuss the ongoing phase III clinical study conducted by the lymphoma study group of the Japan Clinical Oncology Group, which targeted older adults with newly diagnosed multiple myeloma.

The relationship between cost and the recommendation, refusal, and discontinuation of treatment for chronic myeloid leukemia and multiple myeloma in Japan: a cross-sectional exploratory survey

Aims This study aimed to ascertain the number of patients with chronic myelogenous leukemia (CML) and transplant-ineligible patients with multiple myeloma (MM) not recommended by their physicians for optimal drug treatment or who refuse, discontinue, reduce, or skip treatment owing to cost in Japan. Methods A cross-sectional survey was conducted among hematologists, hematologic oncologists, and oncologists in Japan treating ≥1 patient with CML or ≥5 transplant-ineligible patients with MM per year. Results A total of 212 physicians participated: 105 treating patients with CML and 107 treating transplant-ineligible patients with MM. While treatment cost did not lead to non-optimal treatment most patients, physicians reported that they recommended non-optimal treatment to 6.53% of their patients with CML and 1.41% of their transplant-ineligible patients with MM, that 1.51 and 0.35% of their patients, respectively, refused treatment and that 1.97 and 0.71% discontinued treatment owing to treatment cost. However, no significant differences in the effect of treatment cost on recommendation, discontinuation, refusal, or reduction of treatment were observed. Non-recommendation of optimal treatment owing to treatment cost was most common for third-line CML and fourth-line transplant-ineligible MM treatment. Discontinuation due to treatment cost was most common in third-line treatment for both. Conclusion Our results show that non-optimal treatment due to treatment cost occurs among some physicians in Japan for patients with CML and transplant-ineligible patients with MM, but it may be limited to a small percentage of patients. Further research is needed to identify the drivers of treatment decisions for physicians and patients, including those involving treatment cost.

Safety Profile of Ixazomib in Patients with Relapsed/Refractory Multiple Myeloma in Japan: An All-case Post-marketing Surveillance.

Objective To evaluate the safety profile of ixazomib combined with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) in clinical practice in Japan through an all-case post-marketing surveillance. Methods This was a nationwide non-interventional observational study conducted in Japan. The study included all patients who received ixazomib from May 24 to September 24, 2017. Ixazomib was administered to RRMM patients according to the Japanese package insert. All enrolled patients were observed until the completion of the sixth treatment cycle or until ixazomib discontinuation. The patient treatment course, including adverse events (AEs), was reported. Results The safety analysis set included 741 patients; the median age was 71 (range 35-92) years old, and the median number of prior treatment lines was 3 (range 1-30). Adverse drug reactions (ADRs) occurred in 572 (77.2%) patients, most commonly being thrombocytopenia (49.9%), diarrhea (29.2%), and nausea (12.4%). Serious ADRs occurred in 193 (26.0%) patients, most commonly being thrombocytopenia (9.9%) and diarrhea (5.9%). Thrombocytopenia, severe gastrointestinal disorders, infections, skin disorders, and peripheral neuropathy were prespecified as ADRs of clinical importance; the frequency of these ADRs (grade ≥3) were 28.5%, 9.4%, 7.4%, 2.2%, and 1.3%, respectively. Treatment discontinuation was most common with thrombocytopenia and severe gastrointestinal disorders (49 and 43 patients, respectively). Eleven patients died due to ADRs (16 events). Conclusion These results suggest that ixazomib has a tolerable safety profile in clinical practice in Japan. However, close AE management for thrombocytopenia and gastrointestinal disorders should be considered.

A nationwide survey on central nervous system multiple myeloma in Japan: analysis of prognostic and treatment factors that impact survival.

This nationwide multicentre retrospective study was performed to analyze clinical features that predict the prognosis of central nervous system invasion in multiple myeloma (CNS-MM, approximately 1% of MM). Overall, of the 77 adult patients with CNS-MM identified between 2005 and 2016, those diagnosed at MM diagnosis (n=3) had longer overall survival (OS) than those diagnosed at relapse (n=74; median: 48·5 vs 2·7months). Therefore, we compared the relapsed MM with CNS-MM in patients with any treatment (n=60). Multivariate analyses revealed that lenalidomide treatment [hazard ratio (HR) 0·27, P=0·003], intrathecal chemotherapy (IT; HR 0·54, P=0·05), and radiation therapy (RTx; HR 0·33, P<0·001) for CNS-MM had a positive effect on longer OS. These factors were used to develop a scoring system combining the number of treatments with lenalidomide, IT, and RTx (0, 1, 2, 3). The OS of CNS-MM patients was stratified based on these factors, with a median OS of 1·1, 4·5, and 7·5months for patients with zero, one, two to three favourable features, respectively (0 vs 1, P=0·0002; 1 vs 2-3, P=0·08). Multimodal treatment including lenalidomide in addition to conventional IT and RTx can improve OS.

PCN16 Treatment Cost in Patients with Relapsed Refractory Multiple Myeloma in JAPAN

Recent advancements in medical oncology have led to the development of multiple agents for the treatment of relapsed/refractory multiple myeloma (RRMM). These novel agents are generally given as combination therapies and have improved clinical outcomes such as progression-free survival (PFS). Given that patients are recommended for treatment till progression, this may lead to an increase in cost of treatment. The aim of this study was to compare drug treatment costs and drug cost per progression-free life year (PFLY) for the key regimens recommended for RRMM in Japan. List of regimens included in the analysis were based on RRMM treatment guidelines in Japan. These included doublet and triplet regimens containing the following agents: bortezomib (Bort), lenalidomide (Len), ixazomib (Ixa), panobinostat (Pano), carfilzomib (Carf), pomalidomide (Pom), elotuzumab (Elo), daratumumab (Dara), cyclophosphamide (Cyclo) and dexamethasone (Dex). Dosage, dosing schedule, duration of treatment (DOT) and PFS were obtained from published literature. Drug acquisition and administration costs were obtained from regional sources. Costs were cumulated over DOT to estimate per-patient total drug treatment cost which was then divided by PFS duration to estimate drug cost per PFLY for each regimen. The PFS varied from 4 months (PomDex) to 46 months (DaraLenDex). Total drug treatment cost for RRMM showed a wide variation. Drug costs were below ¥10M for BortDex, PomDex, BortCycloDex, and PanBortDex, between ¥10M-¥40M for CarfDex, LenDex, DaraBortDex, IxaLenDex, CarfLenDex and EloLenDex. DaraLenDex had the maximum treatment costs (>¥65M). Drug cost per PFLY ranged from ¥3M for BortCycloDex to ¥23M for EloLenDex. Cost of triplet regimens were generally higher than that for doublet regimens. Drug treatment cost in Japan varies significantly depending upon the regimen being prescribed to a patient with RRMM. Drug treatment cost per PFLY for newer regimens, that are mostly triplets, is substantially higher than doublet regimens.

Current treatment patterns and medical costs for multiple myeloma in Japan: a cross-sectional analysis of a health insurance claims database

Aims: Various drugs have recently been launched for the treatment of multiple myeloma (MM). This increase in the number of treatment options has potentially changed treatment patterns and medical costs for patients with MM. Japanese public health insurance claims were analyzed to examine the change in the treatment patterns of MM drugs and medical costs per patient.Materials and methods: A claims database provided by Medical Data Vision was used, which includes data from ∼20 million patients from >300 acute care hospitals across Japan. The type of MM drugs prescribed and medical costs for patients with MM between April 2008 and December 2016 were examined using monthly cross-sectional analyses. Patients with an International Classification of Diseases, 10th Revision (ICD-10) diagnosis code of C90.0 were classified as having MM. MM drugs were defined by generic names.Results: In total, 19,137 patients with MM (average age at first diagnosis: 69.6 years; percentage of women: 47.9%) were identified from the database. The percentage of patients prescribed each MM drug changed substantially as novel drugs were launched. Total medical costs increased until 2010, then stabilized. MM drug costs increased from approximately 2010, but costs for other care decreased, particularly for hospitalization (including surgery).Limitations: The database contained data from large, acute care hospitals, which may have caused bias in terms of patients’ clinical history and disease severity.Conclusions: Total medical costs for MM have remained stable since 2010. MM drug costs increased, but costs for other care decreased after the launch of lenalidomide in 2010 and other drugs in 2015 and later. More detailed research is required to confirm whether the launch of novel drugs caused the changes in medical costs.

Changing Trends in the Risk Factors of Secondary Primary Malignancies after Autologous Stem Cell Transplantation for Multiple Myeloma before and after the Introduction of Proteasome Inhibitors/Immunomodulatory Agents

Changing Trends in the Risk Factors of Secondary Primary Malignancies after Autologous Stem Cell Transplantation for Multiple Myeloma before and after the Introduction of Proteasome Inhibitors/Immunomodulatory Agents

Phase II Trial of Bortezomib-Based Induction, Autologous Stem Cell Transplantation, Bortezomib-Based Consolidation, and Bortezomib Maintenance in Newly Diagnosed Multiple Myeloma in Japan

Background: Three drug combinations are the standard treatment for newly diagnosed multiple myeloma (NDMM). However, induction, consolidation, and maintenance therapy have not been standardized in Japan. Therefore, in this single arm Phase II study, we evaluated bortezomib-based induction, autologous stem cell transplantation (ASCT), bortezomib-based consolidation, and bortezomib maintenance in transplant eligible NDMM patients and assessed clinical outcomes as well as the minimal residual disease (MRD) status.Methods: Patients received four cycles of CyBorD induction therapy with bortezomib 1.3 mg/m2 and cyclophosphamide 300 mg/m2 on day 1, 8, 15, and 22 and dexamethasone 40 mg on day 1-3, 8-10, 15-17, and 22-24 for the first two cycles and day 1, 8, 15, and 22 for the last two cycles of four 28-day cycles. Peripheral blood stem cells were collected after cyclophosphamide 2 g/m2 for 2 days, which was followed by melphalan 200 mg/m2 and ASCT. Three months after ASCT, patients received consolidation treatment with three cycles of CyBorD identical to the last two cycles of the induction therapy followed by maintenance therapy with bortezomib 1.3 mg/m2 on day 1 and 15 of a 28-day cycle, for 24 months. The primary end-point was the complete response (CR) rate after consolidation therapy and assessed as an interim analysis. Responses were assessed according to the International Myeloma Working Group (IMWG) criteria. MRD was assessed using an allele-specific oligonucleotide real-time quantitative polymerase chain reaction (qPCR). The toxicity was evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).Results: From August 2013 to May 2016, 42 (25 male and 17 female) patients with a median age of 58 (range 42-65) years with NDMM were found eligible and enrolled in 15 centers in Japan. The International Staging System (ISS) values were 1 in 17 (40%), 2 in 20 (48%), and 3 in 5 patients (12%). Adverse cytogenetics of 17p deletion, t(4;14), and t(14;16) were observed in 20%, 18%, and 3% of the evaluable patients, respectively. Following four induction cycles of CyBorD, the overall response rate (ORR) was obtained in 71% of patients, including a CR/sCR of 10% and very good partial response (VGPR) of 26%. One of the evaluable 11 patients showed MRD negativity after induction therapy. Four patients discontinued the protocol during the induction therapy because of grade 4 interstitial pneumonia (n = 2), prolonged grade 3 drug eruption (n = 1), and grade 1 delirium (n = 1). Four patients discontinued the protocol due to doctor judgement (inadequate efficacy, n = 2; repetitive infection, n = 1; grade 3 neutropenia, n = 1). A total of 26 of the 42 patients completed ASCT following the protocol and 18 achieved VGPR/CR, including CR in 10 patients. Three of the evaluable 10 patients showed MRD negativity after ASCT. The 2-year overall and progression-free survival rates were 93% (95% confidence interval [CI], 76%-98%) and 81% (95% CI, 51%-94%), respectively (Figure 1).Conclusions: CyBorD with ASCT for NDMM resulted in relatively high CR rates in the investigated Japanese population, although a relatively high incidence of discontinuation of therapy was observed. Dose and schedule modification of induction therapy may be necessary in Japanese populations. Clinical trial information: UMIN000010542. [Display omitted] DisclosuresImada:Celgene: Honoraria; Bristol-Meyers Squibb: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Nippon Shinyaku: Honoraria; MSD: Honoraria; Chugai: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Kyowa Hakko Kirin: Honoraria; Shire Japan: Honoraria; Ono: Honoraria; Mundipharma: Honoraria. Takaori-Kondo:Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Janssen Pharmaceuticals: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria.

Elotuzumab Plus Pomalidomide/Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma: Japanese Subanalysis of the Randomized Phase 2 Eloquent-3 Study

Elotuzumab Plus Pomalidomide/Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma: Japanese Subanalysis of the Randomized Phase 2 Eloquent-3 Study

Hematologists’ Preferences for First-line Therapy Characteristics for Multiple Myeloma in Japan: Attribute Rating and Discrete Choice Experiment

PurposeWith the progress being made in the treatment of multiple myeloma and other complex cancers, a variety of clinical research and treatment options are being pursued. This study uses a discrete choice experiment (DCE) to estimate treatment characteristic preferences of hematologists in Japan. MethodsA 2-stage process was applied within this study. The first stage is an attribute-rating exercise in which each of the full list of 21 attributes is rated on its importance by the clinicians when selecting a first-line therapy. The top 8 rated attributes from a stepwise logistic regression model are then used to develop a DCE to estimate hematologists’ willingness to trade-off characteristics of the treatment options in their recommendation of a first-line treatment. A logit model was used to identify the attribute levels that were the strongest determinants of the physicians’ treatment preferences. FindingsFrom among the potential treatment attributes presented, improved overall survival had the most significant impact on the treatment choice of participating Japanese hematologists. Improvement in the ability to promptly reduce M-protein is also a highly prioritized treatment characteristic, with hematologists willing to sacrifice just over 1 month extra overall survival for this. Additionally, the hematologists’ value improved suitability for chromosomal abnormalities with poor prognosis, suitability of the mechanism of action in initial treatment, and promptly improving calcium-renal-anemia-bone symptoms each at roughly 0.9 months extended overall survival. The reduction of adverse events is among the other significant factors in choice of treatment, though it was not found to be as strong a determinant as those mentioned. ImplicationsThis study reinforces the expectation that clinical research and treatment options should continue to focus on overall survival and are key priorities in multiple myeloma treatment development. However, clinicians are willing to consider and trade off other clinical factors and markers in their choice of treatment. The potential improvements presented were also found to have a greater impact on treatment choice than aversion to the potential worse outcomes presented.

Pomalidomide with or without dexamethasone for relapsed/refractory multiple myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum.

Determinants of the efficacy and safety of pomalidomide (POM) monotherapy or POM plus dexamethasone (DEX) (POM/DEX) for relapsed and refractory multiple myeloma (RRMM) were examined retrospectively in a real-world clinical practice setting in Japan. The subjects were 108 patients registered with the Kansai Myeloma Forum, who were treated with either POM or POM/DEX. Of these, 79 (73%), 73 (68%), and 58 (54%) were resistant to bortezomib (BTZ), lenalidomide (LEN), and both BTZ and LEN, respectively. The median overall survival (OS) was not reached. The median time to treatment failure (TTF) was 4.4months. The best response was recorded in 96 patients, with a 31% overall response rate (ORR) and a 79% rate of achieving at least stable disease. Number of pre-POM regimens≥5, non-IgG-type M-protein, and time from initial therapy to POM or POM/DEX therapy<2years were associated with shorter TTF and OS. Frequent (>10%) severe adverse events included neutropenia (55.1%), thrombocytopenia (33.7%), anemia (30.6%), febrile neutropenia (12.2%), fatigue (11.2%), and anorexia (10.2%). In conclusion, POM and POM/DEX showed substantial efficacy against RRMM, but new combination therapies with POM are needed to improve efficacy further without causing hematologic toxicities.

Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study.

Background: The aim of this study was to investigate the association of coffee and green tea consumption and the risk of malignant lymphoma and multiple myeloma in a large-scale population-based cohort study in Japan.Methods: In this analysis, a total of 95,807 Japanese subjects (45,937 men and 49,870 women; ages 40-69 years at baseline) of the Japan Public Health Center-based Prospective Study who completed a questionnaire about their coffee and green tea consumption were followed up until December 31, 2012, for an average of 18 years. HRs and 95% confidence intervals were estimated using a Cox regression model adjusted for potential confounders as a measure of association between the risk of malignant lymphoma and multiple myeloma associated with coffee and green tea consumption at baseline.Results: During the follow-up period, a total of 411 malignant lymphoma cases and 138 multiple myeloma cases were identified. Overall, our findings showed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma for both sexes.Conclusions: In this study, we observed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma.Impact: Our results do not support an association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Cancer Epidemiol Biomarkers Prev; 26(8); 1352-6. ©2017 AACR.

Treatment algorithms for multiple myeloma in Japan.

Recent progress in the development of novel therapeutic agents has remarkably improved the treatment outcome for multiple myeloma (MM). Proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib; immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide; the histone deacetylase (HDAC) inhibitor panobinostat; and the monoclonal antibody, elotuzumab, have all been approved in Japan, although only bortezomib and lenalidomide have been approved for initial therapy. Accordingly, the Japanese Society of Hematology has released updated treatment guidelines for MM. Initial treatments with bortezomib-based 2-3 drug regimens and lenalidomide＋dexamethasone are recommended for patients eligible for autologous stem cell transplantation (ASCT), while bortezomib＋melphalan＋prednisolone and lenalidomide＋dexamethasone are recommended for patients who are not eligible for ASCT. These novel agents provide us with wider therapeutic options for relapsed or refractory patients. Consequently, treatment paradigms for MM continue to rapidly evolve, and it is important to select the optimal treatment strategy for each patient.