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1.
Shinsuke Iida Takashi Watanabe Morio Matsumoto Kenshi Suzuki Kazutaka Sunami Tadao Ishida Kiyoshi Ando Takaaki Chou Shuji Ozaki Masafumi Taniwaki Naokuni Uike Hirohiko Shibayama Kiyohiko Hatake Koji Izutsu Takayuki Ishikawa Yoshihisa Shumiya Kensei Tobinai 《Cancer science》2019,110(9):2924-2932
This multicenter, open‐label phase 1/2 study evaluated single‐agent carfilzomib in 50 heavily pretreated Japanese patients with relapsed/refractory multiple myeloma (median of five prior treatments). In phase 1, patients were dosed at three levels: 15, 20, or 20/27 mg/m2. Maximum tolerated dosage was not reached at the tolerability evaluation. Patients in phase 2 were treated with 20/27 mg/m2 carfilzomib. Median duration of exposure to carfilzomib in the 20/27 mg/m2 group at this final analysis was 4.7 months (range: 0.3‐39.4). Overall response rate in the 20/27 mg/m2 group, primary endpoint of the study, was 22.5% (n = 9) (95% confidence interval, 12.3‐37.5) with 2.5% (n = 1) stringent complete response. Median progression‐free survival and overall survival in the 20/27 mg/m2 group were 5.1 months (95% CI, 2.8‐13.6) and 22.9 months (95% CI, 14.1‐not estimable), respectively. Frequently occurring grade ≥3 adverse events in the 20/27 mg/m2 group included lymphopenia (72.5%), neutropenia (40.0%), and leukopenia (32.5%). Giving long‐term carfilzomib monotherapy led to long‐term overall survival for heavily pretreated multiple myeloma patients with a favorable safety profile. Carfilzomib monotherapy can be a good option for heavily pretreated multiple myeloma patients. 相似文献
2.
Ajai Chari Robert F. Cornell Cristina Gasparetto Chatchada Karanes Jeffrey V. Matous Ruben Niesvizky Matthew Lunning Saad Z. Usmani Larry D. Anderson Jr Saurabh Chhabra Saulius Girnius Chaim Shustik Robert Stuart Yihua Lee Zeena Salman Emily Liu Jason Valent 《Hematological oncology》2020,38(3):353-362
Patients with multiple myeloma (MM) inevitably relapse on initial treatment regimens, and novel combination therapies are needed. Ibrutinib is a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, an enzyme implicated in growth and survival of MM cells. Preclinical data suggest supra-additivity or synergy between ibrutinib and proteasome inhibitors (PIs) against MM. This phase 1/2b study evaluated the efficacy and safety of ibrutinib plus the PI carfilzomib and dexamethasone in patients with relapsed/refractory MM (RRMM). In this final analysis, we report results in patients who received the recommended phase 2 dose (RP2D; ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone), which was determined in phase 1. The primary efficacy endpoint was overall response rate (ORR). Fifty-nine patients with RRMM received the RP2D (18 in phase 1 and 41 in phase 2b). These patients had received a median of three prior lines of therapy; 69% were refractory to bortezomib, and 90% were refractory to their last treatment. ORR in the RP2D population was 71% (stringent complete response and complete response: 3% each). Median duration of clinical benefit and median duration of response were both 6.5 months. Median progression-free survival (PFS) was 7.4 months, and median overall survival (OS) was 35.9 months. High-risk patients had comparable ORR and median PFS (67% and 7.7 months, respectively) to non–high-risk patients, whose ORR was 73% and median PFS was 6.9 months, whereas median OS in high-risk patients was 13.9 months and not reached in non–high-risk patients. The most common grade ≥3 hematologic treatment-emergent adverse events (TEAEs) were anemia and thrombocytopenia (17% each); the most common grade ≥3 non-hematologic TEAE was hypertension (19%). In patients with RRMM treated with multiple previous lines of therapy, ibrutinib plus carfilzomib demonstrated anticancer activity within the expected efficacy range. No new safety signals were identified and the combination was well-tolerated. 相似文献
3.
Pomalidomide alone or in combination with dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma
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Kosei Matsue Hiromi Iwasaki Takaaki Chou Kensei Tobinai Kazutaka Sunami Yoshiaki Ogawa Mari Kurihara Shuichi Midorikawa Mohamed Zaki Thomas Doerr Shinsuke Iida 《Cancer science》2015,106(11):1561-1567
This phase 1, open‐label, dose‐escalation study investigated the tolerated dose (recommended dose), safety, efficacy, and pharmacokinetics of pomalidomide alone or pomalidomide plus low‐dose dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma. Twelve patients were enrolled. Patients received pomalidomide 2 mg (Cohort 1) or 4 mg (Cohort 2) orally on day 1 and days 3–21 of a 28‐day cycle. The tolerated dose of pomalidomide was determined to be 4 mg given on days 1–21 of a 28‐day cycle. Efficacy outcomes with pomalidomide plus low‐dose dexamethasone were consistent with those of previous studies. Responses (partial response or better) were achieved by three patients (25%; 1 [17%] in Cohort 1 and 2 [33%] in Cohort 2), and the median time to response was 6.4 months overall (9.0 months for Cohort 1 and 4.2 months for Cohort 2). The median progression‐free survival was 5.5 months overall (5.1 months for Cohort 1 and not reached for Cohort 2). The most frequently occurring grade ≥3 adverse events were neutropenia (67%), anemia (25%), lymphopenia (25%), and pneumonia (25%), consistent with previous studies of pomalidomide plus low‐dose dexamethasone in refractory or relapsed and refractory multiple myeloma. Further investigation of pomalidomide is recommended for Japanese patients with refractory or relapsed and refractory multiple myeloma. This study was registered with ClinicalTrials.gov (NCT01568294). 相似文献
4.
Francesca Gay MD Andreas Günther MD Massimo Offidani MD Monika Engelhardt MD Marco Salvini MD Vittorio Montefusco MD Francesca Patriarca MD Sara Aquino MD Wolfram Pönisch MD Stefano Spada MA Natalie Schub MD Silvia Gentili MD Ralph Wäsch MD Paolo Corradini MD Christian Straka MD Antonio Palumbo MD Hermann Einsele MD Mario Boccadoro MD Pieter Sonneveld MD Martin Gramatzki MD 《Cancer》2021,127(18):3413-3421
5.
Carfilzomib,lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan
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Kenshi Suzuki Masaki Ri Takaaki Chou Isamu Sugiura Naoki Takezako Kazutaka Sunami Tadao Ishida Tohru Izumi Shuji Ozaki Yoshihisa Shumiya Kenji Ota Shinsuke Iida 《Cancer science》2017,108(3):461-468
This is the first study in which the carfilzomib, lenalidomide and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open‐label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM) patients. The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics of the regimen. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15 and 16 of a 28‐day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m2, followed by 27 mg/m2. Lenalidomide and dexamethasone were administered at 25 mg (days 1–21) and 40 mg (days 1, 8, 15 and 22), respectively. Twenty‐six patients were enrolled. Patients had received a median of four prior regimens and 88.5% and 61.5% received previous bortezomib and lenalidomide, respectively. High‐risk cytogenetics were seen in 53.8% of patients. The overall response rate was 88.5%. A higher rate of hyperglycemia was observed than in a previous carfilzomib monotherapy study, but this was attributed to dexamethasone. Carfilzomib pharmacokinetics were not affected by lenalidomide and dexamethasone. The KRd regimen was well tolerated and showed efficacy in Japanese RRMM patients. 相似文献
6.
D S Siegel P Richardson M Dimopoulos P Moreau C Mitsiades D Weber J Houp C Gause S Vuocolo J Eid T Graef K C Anderson 《Blood cancer journal》2014,4(2):e182
The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1–7 and 15–21, 25 mg lenalidomide on days 1–21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed. 相似文献
7.
Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma
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Shinsuke Iida Masashi Wakabayashi Kunihiro Tsukasaki Kenichi Miyamoto Dai Maruyama Kazuhito Yamamoto Yoshifusa Takatsuka Shigeru Kusumoto Junya Kuroda Kiyoshi Ando Yoshitaka Kikukawa Yasufumi Masaki Miki Kobayashi Ichiro Hanamura Hiroaki Asai Hirokazu Nagai Kazuyuki Shimada Norifumi Tsukamoto Yoshiko Inoue Kensei Tobinai 《Cancer science》2018,109(5):1552-1561
A randomized phase II selection design study (JCOG0904) was carried out to evaluate the more promising regimen between bortezomib (Bor) plus dexamethasone (Dex; BD) and thalidomide (Thal) plus Dex (TD) in Bor and Thal‐naïve patients with relapsed or refractory multiple myeloma (RRMM). Patients ≥20 and <80 years old with a documented diagnosis of symptomatic multiple myeloma (MM) who received one or more prior therapies were randomized to receive BD (Bor 1.3 mg/m2) or TD (Thal 200 mg/d). In both arms, 8 cycles of induction (3‐week cycle) were followed by maintenance phase (5‐week cycle) until disease progression, unacceptable toxicity, or patient refusal. The primary end‐point was 1‐year progression‐free survival (PFS). Forty‐four patients were randomized and assigned to receive BD and TD (n = 22, each group). At a median follow‐up of 34.3 months, the 1‐year PFS in the BD and TD arms were 45.5% (95% confidence interval (CI), 24.4%‐64.3%) and 31.8% (95% CI, 14.2%‐51.1%), respectively, and the overall response rates were 77.3% and 40.9%, respectively. The 3‐year overall survival (OS) was 70.0% (95% CI, 44.9%‐85.4%) in the BD, and 48.8% (95% CI, 25.1%‐69.0%) in the TD arm. Among grade 3/4 adverse events, thrombocytopenia (54.5% vs 0.0%) and sensory peripheral neuropathy (22.7% vs 9.1%) were more frequent in BD when compared with the TD arm. Patients treated with BD had better outcomes than those treated with TD with regard to 1‐year PFS and 3‐year OS. Thus, BD was prioritized over TD for further investigations in Bor and Thal‐naïve RRMM patients. (Clinical trial registration no. UMIN000003135.) 相似文献
8.
Predictors of survival outcomes in phase 1 relapsed or refractory multiple myeloma patients
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Meagan S. Barbee PharmD Ajay Nooka MD MPH FACP Jonathan L. Kaufman MD Sungjin Kim MS Zhengjia Chen PhD Leonard T. Heffner MD Jr Sagar Lonial MD R. Donald Harvey PharmD FCCP BCOP 《Cancer》2015,121(6):853-862
9.
Lenalidomide and low‐dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: A phase II study
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Kenshi Suzuki Atsushi Shinagawa Toshiki Uchida Masafumi Taniwaki Hirokazu Hirata Kenichi Ishizawa Kosei Matsue Yoshiaki Ogawa Takayuki Shimizu Maki Otsuka Morio Matsumoto Shinsuke Iida Yasuhito Terui Itaru Matsumura Takashi Ikeda Naoki Takezako Yumi Ogaki Shuichi Midorikawa Vanessa Houck Annette Ervin‐Haynes Takaaki Chou 《Cancer science》2016,107(5):653-658
In the FIRST trial (MM‐020), lenalidomide plus low‐dose dexamethasone (Rd) reduced the risk of disease progression or death compared with combination melphalan–prednisone–thalidomide. As the FIRST trial did not include any Japanese patients, the efficacy and safety of continuous treatment with Rd was evaluated in 26 Japanese patients with newly diagnosed multiple myeloma (NDMM) in a single‐arm, multicenter, open‐label phase II trial (MM‐025). Patients received lenalidomide on days 1–21 of each 28‐day cycle, with a starting dose of 25 mg/day (dose adjusted for renal impairment), and 40 mg/day dexamethasone (dose adjusted for age) on days 1, 8, 15 and 22 of each 28‐day cycle until disease progression or discontinuation for any reason. In the efficacy evaluable population, overall response rate was 87.5%, including 29.2% of patients who achieved a complete response/very good partial response. Median durations of response, progression‐free survival and overall survival have not been reached. The most common grade 3–4 adverse events were neutropenia (23%) and anemia (19%). The efficacy and safety of Rd were consistent with data from larger studies, including the FIRST trial, thereby supporting the use of Rd continuous in Japanese patients with NDMM who are ineligible for stem cell transplantation. 相似文献
10.
Vose JM Panwalkar A Belanger R Coiffier B Baccarani M Gregory SA Facon T Fanin R Caballero D Ben-Yehuda D Giles F 《Leukemia & lymphoma》2007,48(1):39-45
Options for patients with relapsed/refractory lymphoproliferative disorders and multiple myeloma are currently limited. Troxacitabine has shown promise in preclinical studies in a variety of malignancies; hence, the current study was conducted to evaluate the activity of troxacitabine in relapsed or refractory lymphoid malignancies. This was a phase II, open-label, multinational, multicenter study of patients with relapsed or refractory lymphoproliferative disorders or multiple myeloma. Thirty-four adults were enrolled in the study and received the study drug at either 5.4 mg/m2 (n = 16) or 4.3 mg/m2 (n = 18). The dose was decided in a phase I study, during which dose escalation was carried to reach a maximum tolerated dose with an acceptable toxicity profile. Two separate phase I studies were performed in Europe and the US. Troxacitabine was administered by intravenous infusion over 30 min daily for days 1 - 5 every 4 weeks. Treatment was continued to disease progression or until the subjects met criteria for withdrawal or unacceptable toxicities were evident as outlined in the protocol. Two patients had a partial response (PR) to treatment with troxacitabine to yield an overall response rate of 13%. There were no complete responses seen with the drug. Stable disease was achieved in 15 patients (44%). All patients had at least one treatment related adverse event, which led to six withdrawals from the study. Hematologic toxicity constituted the most common adverse events. Serious adverse effects were seen in 62% of patients. None of the 13 deaths were attributed directly to troxacitabine. As a single agent, troxacitabine has limited benefit in patients with advanced lymphoproliferative disorders or multiple myeloma. Future studies will be needed to address modified dosing according to emerging pharmacokinetic and pharmacodynamic data and combination therapy which may lead to improved clinical benefit for troxacitabine in hematologic malignancies. 相似文献
11.
Kazutaka Sunami Kenshi Suzuki Masaki Ri Morio Matsumoto Chihiro Shimazaki Hideki Asaoku Hirohiko Shibayama Kenichi Ishizawa Hiroyuki Takamatsu Takashi Ikeda Dai Maruyama Hitomi Kaneko Michihiro Uchiyama Toru Kiguchi Satoshi Iyama Hirokazu Murakami Keishiro Takahashi Keisuke Tada Sandrine Mac Hlne GuilleminPaveau Shinsuke Iida 《Cancer science》2020,111(12):4526
Isatuximab, an anti‐CD38 monoclonal antibody, targets cells that strongly express CD38 including malignant plasma cells. This open‐label, single‐arm, multicenter, phase 1/2 trial investigated the tolerability/safety and efficacy of isatuximab monotherapy in Japanese patients with heavily pretreated, relapsed/refractory multiple myeloma (RRMM). In Phase 1, patients were sequentially assigned to receive isatuximab once weekly (QW) in cycle 1 (4 weeks) and every 2 weeks (Q2W) in subsequent cycles. Cohort 1 (n = 3) received 10 mg/kg QW/Q2W; cohort 2 (n = 5) received 20 mg/kg QW/Q2W. No dose‐limiting toxicities occurred; the recommended dose for the single‐arm phase 2 study (n = 28) was 20 mg/kg QW/Q2W. The overall safety profile was consistent with the current knowledge of isatuximab. The most common adverse events were infusion reactions (42.9%; 12/28); all were grade 1/2 and generally occurred during the first infusion. The overall response rate with 20 mg/kg QW/Q2W isatuximab was 36.4% (12/33); patients with high‐risk cytogenetic abnormalities had comparable results. In phase 2, the median progression‐free survival was 4.7 (95% confidence interval, 3.75 to not reached) months. Median overall survival was not reached. Isatuximab monotherapy was well tolerated and effective in patients with heavily pretreated RRMM including high‐risk cytogenetic patients. This trial is registered at ClinicalTrials.gov as . NCT02812706相似文献
12.
Meletios Dimopoulos MD Adrian Alegre MD Edward A. Stadtmauer MD Hartmut Goldschmidt MD Jeffrey A. Zonder MD Carlos M. de Castro MD Zvenyslava Masliak MD Donna Reece MD Marta Olesnyckyj RN Zhinuan Yu PhD Donna M. Weber MD 《Cancer》2010,116(16):3807-3814
BACKGROUND:
In patients with multiple myeloma, renal impairment (RI) at the time of diagnosis is associated with poor survival. To the authors' knowledge, the current retrospective analysis presented is the first to assess the impact of various degrees of renal dysfunction on safety and efficacy outcomes in a large cohort of patients with relapsed and/or refractory multiple myeloma who received treatment with lenalidomide plus dexamethasone.METHODS:
Three hundred fifty‐three patients from 2 large phase 3 trials were randomized to receive lenalidomide (25 mg) plus dexamethasone (40 mg). For the purpose of this analysis, RI was defined according to the calculated creatinine clearance (CLCr) level as follows: mild or no RI (CLCr ≥ 60 mL/minute), moderate RI (CLCr from ≥ 30 mL/minute to <60 mL/minute), and severe RI (CLCr <30 mL/minute).RESULTS:
The RI subgroups did not differ significantly in terms of the overall response rate (range, 50%‐64%) or response quality (very good partial response or better, 27%‐37%). In all RI subgroups, the time to progression and progression‐free survival did not differ significantly compared with the mild or no RI group. Patients with RI experienced an increased incidence of thrombocytopenia, required more frequent lenalidomide dose reduction or interruption, and had shorter overall survival than patients with mild or no RI (P = .006). Lenalidomide plus dexamethasone led to improvement in renal function in the majority of patients.CONCLUSIONS:
The results from this study indicated that, with careful monitoring of the CLCr level and adverse events as well as appropriate dose adjustments, lenalidomide plus dexamethasone is an effective and well tolerated treatment option for patients with multiple myeloma who have RI. Cancer 2010. © 2010 American Cancer Society. 相似文献13.
Kazutaka Sunami Kosei Matsue Kenshi Suzuki Naoki Takezako Atsushi Shinagawa Sanae Sakurai Hiromi Tamakoshi Tsvetan Biyukov Teresa Peluso Paul Richardson 《Cancer science》2020,111(6):2116-2122
In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib and dexamethasone (PVd) significantly improved the progression‐free survival (PFS) and the overall response rate (ORR) vs bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma. All patients were previously treated with lenalidomide (70% refractory to lenalidomide) and had received one to three prior regimens. Here we report the first efficacy and safety analysis of PVd vs Vd in Japanese patients with relapsed or refractory multiple myeloma. Seventeen patients enrolled in the OPTIMISMM trial in Japan. With a median follow‐up of 14.8 months, the median PFS was 17.6 months with PVd (n = 12) vs 4.4 months with Vd (n = 5), and the ORR was 100% vs 60.0%, respectively. The safety profile was as expected for PVd. Toxicities were managed with dose reductions and interruptions, and no patients discontinued PVd due to treatment‐emergent adverse events. These results are consistent with those in the overall OPTIMISMM patient population and confirm the clinical benefit of PVd in Japanese patients. 相似文献
14.
Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 (KLF4) was identified as a contributing factor. Expression levels as well as nuclear localization of KLF4 protein were elevated in MM cells with acquired carfilzomib resistance. Chromatin immunoprecipitations indicated that endogenous KLF4 bound to the promoter regions of the SQSTM1 gene encoding the ubiquitin-binding adaptor protein sequestosome/p62 that links the proteasomal and autophagic protein degradation pathways. Ectopic expression of KLF4 induced upregulation of SQSTM1. On the other hand, inhibitors of autophagy sensitized MM cells to carfilzomib, even in carfilzomib-resistant derivatives having increased expression of the multidrug resistance protein P-glycoprotein. Thus, we report here a novel function for KLF4, one of the Yamanaka reprogramming factors, as being a contributor to autophagy gene expression which moderates preclinical proteasome inhibitor efficacy in MM. 相似文献
15.
Sherif S. Farag Shuhong Zhang Buffy S. Jansak Xiaojing Wang Eric Kraut Kenneth Chan Janet E. Dancey Michael R. Grever 《Leukemia research》2009,33(11):1475-1480
In a phase II trial, 16 patients with relapsed refractory multiple myeloma received temsirolimus 25 mg I.V. weekly until progression. One partial response and 5 minor responses were observed for a total response rate of 38%. The median time to progression was 138 days. Grade 3–4 toxicity included fatigue (n = 3), neutropenia (n = 2), thrombocytopenia (n = 2), interstitial pneumonitis (n = 1), stomatitis (n = 1) and diarrhea (n = 1). Clinical activity was associated with a higher area under the curve (AUC) and maximal reduction in phosphorylated p70S6K and 4EBP1 in peripheral blood mononuclear cells. At the dose and schedule used, temsirolimus had low single agent activity. Investigation of alternate dosing schedules and use in combinations is indicated. 相似文献
16.
沙利度胺治疗难治性复发性多发性骨髓瘤的临床研究 总被引:7,自引:0,他引:7
目的:观察沙利度胺(Thalidomide,国内商品名:反应停)单药或联合地塞米松治疗多发性骨髓瘤(Multiple Myeloma,MM)的疗效及副作用。方法:单药组:男性13例,女性2例,中位年龄58岁。其中2例为初发的MM;1例为原发性浆细胞白血病(PCL);12例为难治性MM,其中3例为自体外周血干细胞移植(AutoPBSCT)术后复发。反应停治疗起始剂量为100mg/d,根据患者耐受情况,逐渐加量,最高达800mg/d。联合组:男性20例,女性7例,中位年龄56岁。其中初发1例;1例为原发性PCL;25例为难治MM,其中2例为自体外周血干细胞移植(AutoPBSCT)术后复发。反应停剂量为400mg/d左右加用地塞米松40mg/天,第1~4天,第9~12天,第17~20天,1个月为一个疗程。结果:单药组42.9%(6/14)的患者对治疗有效,其中3例为完全缓解(CR)或接近完全缓解(Near-CR),1例有明显治疗反应(Major response),1例为部分缓解(PR)。12例难治性MM中4例有效(33.3%);联合组有效率为57.7%(15/26),其中4例为CR或Near-CR,2例有明显治疗反应,9例为PR。25例难治性MM中11例有效(44.0%)。两组间在总有效率及难治病例的有效率方面均无显著差异。两组患者均出现不同程度的便秘、皮疹等副作用,但均可耐受。结论:沙利度胺单药或联合地塞米松对难治性复发性MM均有效。 相似文献
17.
Masaki Ri Kenshi Suzuki Tadao Ishida Junya Kuroda Taku Tsukamoto Takanori Teshima Hideki Goto Carolyn C. Jackson Huabin Sun Lida Pacaud Ei Fujikawa TzuMin Yeh Tomoyoshi Hatayama Kensuke Aida Yoshihiro Sunagawa Shinsuke Iida 《Cancer science》2022,113(12):4267
Chimeric antigen receptor (CAR) T cells targeting B‐cell maturation antigen have shown positive responses in patients with multiple myeloma (MM). The phase 2 portion of the CARTITUDE‐1 study of ciltacabtagene autoleucel (cilta‐cel) included a cohort of Japanese patients with relapsed/refractory MM. Following a conditioning regimen of cyclophosphamide (300 mg/m2) and fludarabine (30 mg/m2), patients received a single cilta‐cel infusion at a target dose of 0.75 × 106 (range, 0.5–1.0 × 106CAR‐positive viable T cells/kg). The primary endpoint was overall response rate (ORR; defined as partial response or better) by International Myeloma Working Group criteria. A key secondary endpoint was the rate of very good partial response (VGPR) or better (defined as VGPR, complete response, stringent complete response). This first analysis was performed at 6 months after the last patient received cilta‐cel. Thirteen patients underwent apheresis, nine of whom received cilta‐cel infusion. Eight patients who received cilta‐cel at the target dose responded, yielding an ORR of 100%. Seven of eight (87.5%) patients achieved a VGPR or better. One additional patient who received a below‐target dose of cilta‐cel also achieved a best response of VGPR. MRD negativity (10−5 threshold) was achieved in all six evaluable patients. Eight of nine (88.9%) patients who received cilta‐cel infusion experienced a grade 3 or 4 adverse event, and eight (88.9%) patients experienced cytokine release syndrome (all grade 1 or 2). No CAR‐T cell neurotoxicity was reported. A positive benefit/risk profile for cilta‐cel was established for heavily pretreated Japanese patients with relapsed or refractory MM. 相似文献
18.
Kai Neben Mathias Witzens‐Harig Ines Gütgemann Marc‐Steffen Raab Thomas Moehler Ingo GH Schmidt‐Wolf 《Hematological oncology》2013,31(4):197-200
Sorafenib is a small molecular inhibitor of several tyrosine protein kinases, including vascular endothelial growth factor receptor, platelet‐derived growth factor receptor and rapidly accelerated fibrosarcoma kinases, targeting signal transduction and angiogenic pathways. It is approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma. The objectives of this prospective phase II trial were to assess the activity and tolerability of sorafenib in patients with recurrent or refractory myeloma. In total, 11 patients were enrolled. Patients received 2 × 200 mg of sorafenib orally twice daily until completing 13 full cycles or disease progression. Of the side effects, 8.8% grade 3 and 1.1% grade 4 occurred. Sorafenib treatment was effective in two patients who achieved a partial response and a continuous stable disease with duration of 24.4 months and 6.9 month, respectively. Further clinical investigations are recommended to investigate sorafenib single agent activity in myeloma subgroups with ras‐/BRAF‐/vascular endothelial growth factor receptor pathway activation and combination therapy approaches. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
19.
BACKGROUND: The purpose of the current study was to evaluate the efficacy and toxicity of weekly bortezomib in the treatment of patients with recurrent/refractory multiple myeloma. METHODS: A total of 40 patients with multiple myeloma who had received either 1 or 2 previous treatment regimens were treated with bortezomib at a dose of 1.6 mg/m(2) intravenously for 4 consecutive weeks, followed by 1 week without treatment. Responses were measured using International Myeloma Working Group criteria. RESULTS: Twenty-two patients (55%; 95% confidence interval, 40%-70%) achieved objective responses to treatment, with a median response duration of 16 months. The median progression-free survival for all patients was 9.6 months, with a 1-year progression-free survival rate of 39%. The 1-year and 2-year overall survival rates were 75% and 51%, respectively. Weekly bortezomib was generally well tolerated; grade 3/4 (using the National Cancer Institute Common Toxicity Criteria [version 3.0]) neutropenia (13%), thrombocytopenia (20%), fatigue (15%), diarrhea (13%), and neuropathy (10%) were experienced by a minority of patients. CONCLUSIONS: In the current study, a schedule of weekly bortezomib was found to be effective and well tolerated in patients with previously treated multiple myeloma. Although the response rate and duration appear comparable to those achieved with twice-weekly bortezomib, the relative efficacy of these 2 schedules cannot be determined definitively on the basis of this phase 2 study. A weekly schedule of bortezomib is a reasonable option for patients who have logistic difficulties receiving a twice-weekly schedule, and is an attractive schedule for incorporation into combination regimens. 相似文献
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Thomas G. Martin MD Nina Shah MD Joshua Richter MD David H. Vesole MD Sandy W. Wong MD Chiung-Yu Huang PhD Deepu Madduri MD Sundar Jagannath MD David S. Siegel MD Noa Biran MD Jeffrey L. Wolf MD Samir Parekh MD Hearn J. Cho MD PhD Pamela Munster MD Shambavi Richard MD Samira Ziti-Ljajic MSc Ajai Chari MD 《Cancer》2021,127(11):1816-1826