New uniform response criteria are required to adequately assess clinical outcomes in myeloma. The European Group for Blood and Bone Marrow Transplant/International Bone Marrow Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system. Categories for stringent complete response and very good partial response are added. The serum free light-chain assay is included to allow evaluation of patients with oligo-secretory disease. Inconsistencies in prior criteria are clarified making confirmation of response and disease progression easier to perform. Emphasis is placed upon time to event and duration of response as critical end points. The requirements necessary to use overall survival duration as the ultimate end point are discussed. It is anticipated that the International Response Criteria for multiple myeloma will be widely used in future clinical trials of myeloma.

International uniform response criteria for multiple myeloma

Improved survival in multiple myeloma and the impact of novel therapies

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebocontrolled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation. METHODS:We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival. RESULTS:Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β 2- microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P = 0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001). CONCLUSIONS:Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.) Copyright © 2012 Massachusetts Medical Society.

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Lenalidomide Maintenance after Stem-Cell Transplantation for Multiple Myeloma

https://www.mayoclinicproceedings.org/article/S0025-6196(11)60296-6/pdf

Management of Newly Diagnosed Symptomatic Multiple Myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines

Purpose To compare efficacy and safety of bortezomib plus dexamethasone and vincristine plus doxorubicin plus dexamethasone (VAD) as induction before stem-cell transplantation in previously untreated myeloma. Patients and Methods Four hundred eighty-two patients were randomly assigned to VAD (n 121), VAD plus dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) consolidation (n 121), bortezomib plus dexamethasone (n 121), or bortezomib plus dexamethasone plus DCEP (n 119), followed by autologous stem-cell transplantation. Patients not achieving very good partial response (VGPR) required a second transplantation. The primary end point was postinduction complete response/near complete response (CR/nCR) rate. Results Postinduction CR/nCR (14.8% v 6.4%), at least VGPR (37.7% v 15.1%), and overall response (78.5% v 62.8%) rates were significantly higher with bortezomib plus dexamethasone versus VAD; CR/nCR and at least VGPR rates were higher regardless of disease stage or adverse cytogenetic abnormalities. Response rates were similar in patients who did and did not receive DCEP. Post first transplantation, CR/nCR (35.0% v 18.4%) and at least VGPR (54.3% v 37.2%) rates remained significantly higher with bortezomib plus dexamethasone. Median progression-free survival (PFS) was 36.0 months versus 29.7 months (P .064) with bortezomib plus dexamethasone versus VAD; respective 3-year survival rates were 81.4% and 77.4% (median follow-up, 32.2 months). The incidence of severe adverse events appeared similar between groups, but hematologic toxicity and deaths related to toxicity (zero v seven) were more frequent with VAD. Conversely, rates of grade 2 (20.5% v 10.5%) and grades 3 to 4 (9.2% v 2.5%) peripheral neuropathy during induction through first transplantation were significantly higher with bortezomib plus dexamethasone. Conclusion Bortezomib plus dexamethasone significantly improved postinduction and post-transplantation CR/nCR and at least VGPR rates compared with VAD and resulted in a trend for longer PFS. Bortezomib plus dexamethasone should therefore be considered a standard of care in this setting. J Clin Oncol 28:4621-4629. © 2010 by American Society of Clinical Oncology

https://ascopubs.org/doi/pdf/10.1200/jco.2009.27.9158

Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial.

Purpose Results of a prospective randomized trial conducted by the Intergroupe Francais du Myelome (IFM 90) indicated that autologous hematopoietic cell–supported high-dose therapy (HDT) effected higher complete response rates and extended progression-free survial (PFS) and overall survival (OS) compared with standard-dose therapies (SDT) for patients with multiple myeloma (MM). Patients and Methods In 1993, three North American cooperative groups launched a prospective randomized trial (S9321) comparing HDT (melphalan [MEL] 140 mg/m2 plus total-body irradiation 12 Gy) with SDT using the vincristine, carmustine, MEL, cyclophosphamide, and prednisone regimen. Responders on both arms (≥ 75%) were randomly assigned to interferon (IFN) or no maintenance treatment. Results With a median follow-up time of 76 months, no differences were observed in response rates between the two study arms (HDT, n = 261 patients; SDT, n = 255 patients). Similarly, PFS and OS durations did not differ between the HDT and SDT arms,...

Standard Chemotherapy Compared With High-Dose Chemoradiotherapy for Multiple Myeloma: Final Results of Phase III US Intergroup Trial S9321

Purpose: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non‐small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. Patients and Methods: Two hundred two patients received VC (vinorelbine 25 mg/m 2 /wk and cisplatin 100 mg/m 2 /d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m 2 over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. Results: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P 5 .002) and neutropenia (P 5 .008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P 5 .001, P 5 .007), and grade 3 peripheral neuropathy was higher on the PC arm (P < .001). More patients on the VC arm discontinued therapy because of toxicity (P 5 .001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. Conclusion: PC is equally efficacious as VC for the treatment of advanced non‐small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued. J Clin Oncol 19:3210-3218. © 2001 by American Society of Clinical Oncology.

Randomized P hase I II T rial o f P aclitaxel P lus C arboplatin Versus V inorelbine P lus C isplatin i n t he T reatment o f Patients W ith A dvanced N on-Small-Cell L ung C ancer: A Southwest O ncology G roup T rial

Dennis F. Moore

Papers

Standard Chemotherapy Compared With High-Dose Chemoradiotherapy for Multiple Myeloma: Final Results of Phase III US Intergroup Trial S9321

Randomized P hase I II T rial o f P aclitaxel P lus C arboplatin Versus V inorelbine P lus C isplatin i n t he T reatment o f Patients W ith A dvanced N on-Small-Cell L ung C ancer: A Southwest O ncology G roup T rial