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Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18–9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower β2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/μL), non-deviated κ/λ ratio (0.1–10), lower B2MG (p p

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Supplemental material, sj-docx-13-tah-10.1177_20406207221142487 for Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide by Yutaka Shimazu, Junya Kanda, Hitomi Kaneko, Kazunori Imada, Ryosuke Yamamura, Satoru Kosugi, Yuji Shimura, Tomoki Ito, Shin-ichi Fuchida, Hitoji Uchiyama, Kentaro Fukushima, Satoshi Yoshihara, Hitoshi Hanamoto, Hirokazu Tanaka, Nobuhiko Uoshima, Kensuke Ohta, Hideo Yagi, Hirohiko Shibayama, Yoshiyuki Onda, Yasuhiro Tanaka, Yoko Adachi, Mitsuhiro Matsuda, Masato Iida, Takashi Miyoshi, Toshimitsu Matsui, Ryoichi Takahashi, Teruhito Takakuwa, Masayuki Hino, Naoki Hosen, Shosaku Nomura, Chihiro Shimazaki, Itaru Matsumura, Akifumi Takaori-Kondo, Junya Kuroda in Therapeutic Advances in Hematology

Supplemental material, sj-docx-15-tah-10.1177_20406207221142487 for Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide by Yutaka Shimazu, Junya Kanda, Hitomi Kaneko, Kazunori Imada, Ryosuke Yamamura, Satoru Kosugi, Yuji Shimura, Tomoki Ito, Shin-ichi Fuchida, Hitoji Uchiyama, Kentaro Fukushima, Satoshi Yoshihara, Hitoshi Hanamoto, Hirokazu Tanaka, Nobuhiko Uoshima, Kensuke Ohta, Hideo Yagi, Hirohiko Shibayama, Yoshiyuki Onda, Yasuhiro Tanaka, Yoko Adachi, Mitsuhiro Matsuda, Masato Iida, Takashi Miyoshi, Toshimitsu Matsui, Ryoichi Takahashi, Teruhito Takakuwa, Masayuki Hino, Naoki Hosen, Shosaku Nomura, Chihiro Shimazaki, Itaru Matsumura, Akifumi Takaori-Kondo, Junya Kuroda in Therapeutic Advances in Hematology

Supplemental material, sj-docx-14-tah-10.1177_20406207221142487 for Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide by Yutaka Shimazu, Junya Kanda, Hitomi Kaneko, Kazunori Imada, Ryosuke Yamamura, Satoru Kosugi, Yuji Shimura, Tomoki Ito, Shin-ichi Fuchida, Hitoji Uchiyama, Kentaro Fukushima, Satoshi Yoshihara, Hitoshi Hanamoto, Hirokazu Tanaka, Nobuhiko Uoshima, Kensuke Ohta, Hideo Yagi, Hirohiko Shibayama, Yoshiyuki Onda, Yasuhiro Tanaka, Yoko Adachi, Mitsuhiro Matsuda, Masato Iida, Takashi Miyoshi, Toshimitsu Matsui, Ryoichi Takahashi, Teruhito Takakuwa, Masayuki Hino, Naoki Hosen, Shosaku Nomura, Chihiro Shimazaki, Itaru Matsumura, Akifumi Takaori-Kondo, Junya Kuroda in Therapeutic Advances in Hematology

Supplemental material, sj-docx-15-tah-10.1177_20406207221142487 for Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide by Yutaka Shimazu, Junya Kanda, Hitomi Kaneko, Kazunori Imada, Ryosuke Yamamura, Satoru Kosugi, Yuji Shimura, Tomoki Ito, Shin-ichi Fuchida, Hitoji Uchiyama, Kentaro Fukushima, Satoshi Yoshihara, Hitoshi Hanamoto, Hirokazu Tanaka, Nobuhiko Uoshima, Kensuke Ohta, Hideo Yagi, Hirohiko Shibayama, Yoshiyuki Onda, Yasuhiro Tanaka, Yoko Adachi, Mitsuhiro Matsuda, Masato Iida, Takashi Miyoshi, Toshimitsu Matsui, Ryoichi Takahashi, Teruhito Takakuwa, Masayuki Hino, Naoki Hosen, Shosaku Nomura, Chihiro Shimazaki, Itaru Matsumura, Akifumi Takaori-Kondo, Junya Kuroda in Therapeutic Advances in Hematology

Supplemental material, sj-docx-14-tah-10.1177_20406207221142487 for Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide by Yutaka Shimazu, Junya Kanda, Hitomi Kaneko, Kazunori Imada, Ryosuke Yamamura, Satoru Kosugi, Yuji Shimura, Tomoki Ito, Shin-ichi Fuchida, Hitoji Uchiyama, Kentaro Fukushima, Satoshi Yoshihara, Hitoshi Hanamoto, Hirokazu Tanaka, Nobuhiko Uoshima, Kensuke Ohta, Hideo Yagi, Hirohiko Shibayama, Yoshiyuki Onda, Yasuhiro Tanaka, Yoko Adachi, Mitsuhiro Matsuda, Masato Iida, Takashi Miyoshi, Toshimitsu Matsui, Ryoichi Takahashi, Teruhito Takakuwa, Masayuki Hino, Naoki Hosen, Shosaku Nomura, Chihiro Shimazaki, Itaru Matsumura, Akifumi Takaori-Kondo, Junya Kuroda in Therapeutic Advances in Hematology

Supplemental material, sj-docx-13-tah-10.1177_20406207221142487 for Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide by Yutaka Shimazu, Junya Kanda, Hitomi Kaneko, Kazunori Imada, Ryosuke Yamamura, Satoru Kosugi, Yuji Shimura, Tomoki Ito, Shin-ichi Fuchida, Hitoji Uchiyama, Kentaro Fukushima, Satoshi Yoshihara, Hitoshi Hanamoto, Hirokazu Tanaka, Nobuhiko Uoshima, Kensuke Ohta, Hideo Yagi, Hirohiko Shibayama, Yoshiyuki Onda, Yasuhiro Tanaka, Yoko Adachi, Mitsuhiro Matsuda, Masato Iida, Takashi Miyoshi, Toshimitsu Matsui, Ryoichi Takahashi, Teruhito Takakuwa, Masayuki Hino, Naoki Hosen, Shosaku Nomura, Chihiro Shimazaki, Itaru Matsumura, Akifumi Takaori-Kondo, Junya Kuroda in Therapeutic Advances in Hematology

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Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib–lenalidomide–dexamethasone (KRd) and carfilzomib–dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered.

Background: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. Objectives: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. Design: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. Methods: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. Results: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG Conclusion: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for

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Introduction: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. Patients and Methods: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. Results: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. Conclusion: These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.