Treatment with BEACOPP, as compared with ABVD, resulted in better initial tumor control, but the long-term clinical outcome did not differ significantly between the two regimens. (Funded by Fondazione Michelangelo; ClinicalTrials.gov number, NCT01251107.).
High-dose therapy is an effective standard treatment for multiple myeloma patients. Evidence that intermediate-dose therapy improves survival is limited. At diagnosis, about 70% of patients are older than 65. Intermediate-dose regimen is very well tolerated in older patients. In a multicenter study, 194 patients were randomized to receive at diagnosis either conventional chemotherapy (6 courses of oral melphalan and prednisone [MP]) or intermediate-dose therapy (2 courses of melphalan at 100 mg/m 2 [MEL100]) with stem cell support. Response rate was higher after MEL100. Near-complete remission (nCR) was 6% after MP and 25% after MEL100 (P ؍ .0002). At 3 years, MEL100 increased event-free survival (EFS) from 16% to 37% and overall survival (OS) from 62% to 77% (P < .001). Similar results were observed in patients aged 65 to 70: nCR was 8% after MP and 25% after MEL100 (P ؍ .05); at 3 years, MEL100 improved EFS from 18% to 31% (P ؍ .01) and OS from 58% to 73% (P ؍ .01). Patients aged 65 to 70 had a median OS of 37.2 months (MP) versus 58 months (MEL100
PURPOSE We investigated the effect on minimal residual disease, by qualitative and real-time quantitative polymerase chain reaction (RQ-PCR), of a consolidation regimen that included bortezomib, thalidomide, and dexamethasone (VTD) in patients with multiple myeloma (MM) responding to autologous stem-cell transplantation (auto-SCT). PATIENTS AND METHODS Patients achieving at least very good partial response who had an available molecular marker based on the immunoglobulin heavy-chain rearrangement received four courses of treatment every month: four infusions per month of bortezomib at 1.6 mg/m(2), thalidomide at 200 mg/d, and dexamethasone at 20 mg/d on days 1 to 4, 8 to 11, and 15 to 18. Patients were studied with tumor-clone-specific primers by qualitative nested PCR and RQ-PCR. Results Of 39 patients enrolled, 31 received the four VTD courses. Immunofixation complete responses increased from 15% after auto-SCT to 49% after VTD. Molecular remissions (MRs) were 3% after auto-SCT and 18% after VTD. Median time to maximum response was 3.5 months. So far, no patient in MR has relapsed (median follow-up, 42 months). VTD consolidation induced an additional depletion of 4.14 natural logarithms of tumor burden by RQ-PCR. Patients with a tumor load less than the median value after VTD had outcomes better than those who had tumor loads above the median value after VTD (at median follow-up: progression-free survival, 100% v 57%; P < .001). CONCLUSION To the best of our knowledge, this study is the first to document the occurrence of persistent MRs in a proportion of MM patients treated without allogeneic transplantation. Moreover, the major reduction in tumor load recorded by RQ-PCR after VTD suggests that unprecedented levels of tumor cell reduction can be achieved in MM thanks to the new nonchemotherapeutic drugs.
Funding information BolognAIL, AIRCThe most frequent BCR-ABL1 fusion transcripts in chronic myeloid leukemia (CML) are the e13a2 (b2a2) and the e14a2 (b3a2) ones. In the imatinib era few studies addressing the prognostic significance of the BCR-ABL1 transcript type in early chronic phase CML have been published. Overall, these studies suggest that in e14a2 patients the response to imatinib is faster and deeper. To evaluate if the BCR-ABL1 transcript type (e13a2 compared to e14a2) affect the response to imatinib and the clinical outcome in newly diagnosed adult CML patients, 559 patients enrolled in 3 prospective studies (NCT00514488, NCT00510926, observational study CML/023) were analyzed. A qualitative PCR was performed at baseline: 52% patients had a e14a2 transcript, 37% a e13a2 transcript, 11% co-expressed both transcripts and 1% had other rare transcripts. The median follow-up was 76 months (95% of the patients had at least a 5-year observation). The complete cytogenetic response rates were comparable in e14a2 and e13a2 patients. The median time to MR 3.0 (6 and 12 months) and MR 4.0 (41 and 61 months) was significantly shorter for e14a2 patients compared to e13a2 patients, with a higher cumulative probability of MR 3.0 (88% and 83%, P < .001) and MR 4.0 (67% and 52%, P 5 .001). The 7-year overall survival (90% and 83%, P 5 .017), progression-free survival (89% and 81%, P 5 .005) and failure-free survival (71% and
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