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Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0–100 days, 101 days–1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4–108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and <2.31 cases per 100 patient-years from the 101st day. At 100 days after ASC T, 45.7% of patients had complications, with infectious events being twice as frequent as non-infectious complications. Bacterial infections (6.5 cases per 100 patient-years, 95% CI: 6.1–7.0) and gastrointestinal complications (4.7 cases per 100 patient-years, 95% CI: 4.3–5.1) were the most common early events. The pattern of complications changed with time from ASCT. The presence of complications after ASCT was not associated with overall survival. Conclusions: Our data provide a solid basis for comparing ASCT-related complications to those caused by emerging treatments in multiple myeloma, such as CAR T-cell therapy and other immunotherapies. [ABSTRACT FROM AUTHOR]

Treatment discontinuation due to adverse events (AEs) occurred more frequently in patients treated with ITd (17%), mostly due to PN (6%), as compared with those who received Id (10%), ICd (12%), or IBd (9%; Fig. Id ixazomib-dexamethasone, ICd ixazomib-cyclophosphamide-dexamethasone, ITd ixazomib-thalidomide-dexamethasone, IBd ixazomib-bendamustine-dexamethasone. Bortezomib is a backbone of induction therapies for older patients with multiple myeloma (MM), either in combination with lenalidomide-dexamethasone (VRd) or with daratumumab-melphalan-prednisone (DVMP) [[1]]. During the induction phase, ixazomib dose reductions were more common in patients receiving triplets (ICd, 24%; ITd, 20%; IBd, 18%) than in those treated with Id (2%). [Extracted from the article]

Objectives: Autologous stem cell transplantation is the gold standard for eligible newly diagnosed multiple myeloma patients. Patients are usually hospitalized for administration of mobilization chemotherapy. We aimed to assess safety and efficacy of mobilization therapy with low‐dose (2 g/m2) and intermediate‐dose (3‐4 g/m2) cyclophosphamide administered as outpatient. Methods: A total of 176 consecutive newly diagnosed transplant‐eligible myeloma patients receiving outpatient mobilization were retrospectively evaluated. Induction therapy was mainly performed with new drugs (91%). Results: Chemotherapy was very well tolerated with 16.6% of patients having all‐grade adverse events (AEs) and only 1.2% having severe AEs. The most frequently reported AEs were nausea and vomiting grade 1‐2 (6.8%). Only 5.7% of patients required hospitalization for AEs. Stem cell collection was successful in 93.1% of patients, with a median CD34+ harvest of 8.7 × 106/kg. Target for 2 autologous stem cell transplantation (at least 6 CD34+ × 106/kg) was reached by 76.3% of patients. Administration of plerixafor on demand was necessary in 12.1% of patients. Conclusions: Outpatient mobilization with low‐ and intermediate‐dose cyclophosphamide appears an efficient and safe procedure, with minimal and manageable AEs and low rate of hospitalization. [ABSTRACT FROM AUTHOR]

Patients with newly diagnosed multiple myeloma and high-risk cytogenetic abnormalities (HRCA) represent an unmet medical need. In the FORTE trial, lenalidomide and dexamethasone plus carfilzomib (KRd) induction resulted in a higher proportion of patients with at least a very good partial response as compared with carfilzomib, cyclophosphamide, and dexamethasone (KCd), and carfilzomib plus lenalidomide maintenance prolonged progression-free survival compared with lenalidomide maintenance. In this prespecified analysis of the FORTE trial, we described the outcomes of enrolled patients according to their cytogenetic risk. The UNITO-MM-01/FORTE was a randomised, open-label, phase 2 trial done at 42 Italian academic and community practice centres, which enrolled transplant-eligible patients with newly diagnosed multiple myeloma aged 18–65 years. Eligible patients had newly diagnosed multiple myeloma based on standard International Myeloma Working Group criteria, a Karnofsky performance status of at least 60%, and had not received any previous treatment with anti-myeloma therapy. At enrolment, patients were stratified according to International Staging System stage (I vs II/III) and age (<60 years vs 60–65 years) and randomly assigned (1:1:1) to KRd plus autologous stem-cell transplantation (ASCT; four 28-day induction cycles with KRd, melphalan at 200 mg/m2 and ASCT [MEL200-ASCT], followed by four 28-day KRd consolidation cycles), 12 28-day KRd cycles, or KCd plus ASCT (four 28-day induction cycles with KCd, MEL200-ASCT, and four 28-day KCd consolidation cycles), using a web-based system (block randomisation, block size of 12). Carfilzomib was administered at 20 mg/m2 on days 1 and 2 of cycle 1, followed by 36 mg/m2 intravenously administered on days 8, 9, 15, and 16 of cycle 1, and then 36 mg/m2 intravenously administered for all subsequent doses on days 1, 2, 8, 9, 15, 16; lenalidomide 25 mg was administered orally on days 1–21; cyclophosphamide 300 mg/m2 was administered orally on days 1, 8, and 15; and dexamethasone 20 mg was administered orally or intravenously on days 1, 2, 8, 9, 15, 16, 22, and 23. After the consolidation phase, patients were stratified according to induction–consolidation treatment and randomly assigned (1:1; block size of 8) to maintenance treatment with carfilzomib plus lenalidomide or lenalidomide alone. Carfilzomib 36 mg/m2 was administered intravenously on days 1–2 and days 15–16, every 28 days for up to 2 years, and lenalidomide 10 mg was administered orally on days 1–21 every 28 days until progression or intolerance in both groups. The primary endpoints were the proportion of patients with at least a very good partial response after induction with KRd versus KCd and progression-free survival with carfilzomib plus lenalidomide versus lenalidomide alone as maintenance treatment. In this preplanned analysis, we included patients enrolled in the FORTE trial with complete cytogenetic data on del(17p), t(4;14), t(14;16), del(1p), gain(1q) (3 copies), and amp(1q) (≥4 copies) assessed by fluorescence in-situ hybridisation analysis on CD138-positive sorted cells. We assessed progression-free survival, overall survival, minimal residual disease negativity, and 1-year sustained minimal residual disease negativity according to the presence of zero, one, and two or more HRCA across treatment groups. The FORTE trial is ongoing, and registered with ClinicalTrials.gov , NCT02203643. Between Feb 23, 2015, and April 5, 2017, 477 patients were enrolled, of whom 396 (83%) had complete cytogenetic data and were analysed (176 [44%] of whom were women and 220 [56%] were men). The median follow-up from first randomisation was 51 months (IQR 46–56). 4-year progression-free survival was 71% (95% CI 64–78) in patients with zero HRCA, 60% (95% CI 52–69) in patients with one HRCA, and 39% (95% CI 30–50) in patients with two or more HRCA. Compared with patients with zero HRCA, the risk of progression or death was similar in patients with one HRCA (hazard ratio [HR] 1·33 [95% CI 0·90–1·97]; p=0·15) and higher in patients with two or more HRCA (HR 2·56 [95% CI 1·74–3·75]); p<0·0001) across the induction–intensification–consolidation groups. Moreover, the risk of progression or death was also higher in patients with two or more HRCA versus those with one HRCA (HR 1·92 [95% CI 1·34–2·76]; p=0·0004). 4-year overall survival from the first randomisation was 94% (95% CI 91–98) in patients with zero HRCA, 83% (95% CI 76–90) in patients with one HRCA, and 63% (95% CI 54–74) in patients with two or more HRCA. Compared with patients with zero HRCA, the risk of death was significantly higher in patients with one HRCA (HR 2·55 [95% CI 1·22–5·36]; p=0·013) and two or more HRCA (HR 6·53 [95% CI 3·24–13·18]; p<0·0001). Patients with two or more HRCA also had a significantly higher risk of death than those with one HRCA (HR 2·56 [95% CI 1·53–4·28]; p=0·0004). The rates of 1-year sustained minimal residual disease negativity were similar in patients with zero HRCA (53 [35%] of 153] and with one HRCA (57 [41%] of 138) and were lower in patients with two or more HRCA (25 [24%] of 105). The median duration of follow-up from second randomisation was 37 months (IQR 33–42). 3-year progression-free survival from the second randomisation was 80% (95% CI 74–88) in patients with zero HRCA, 68% (95% CI 59–78) in patients with one HRCA, and 53% (95% CI 42–67) in patients with two or more HRCA. The risk of progression or death was higher in patients with one HRCA (HR 1·68 [95% CI 1·01–2·80]; p=0·048) and two or more HRCA (2·74 [95% CI 1·60–4·69], p=0·0003) than in patients with zero HRCA. This preplanned analysis of the FORTE trial showed that carfilzomib-based induction–intensification–consolidation regimens are effective strategies in patients with standard risk (zero HRCA) and high-risk (one HRCA) myeloma, resulting in similar rates of progression-free survival and 1-year sustained minimal residual disease negativity. Despite promising progression-free survival, patients with ultra-high-risk disease (those with 2 or more HRCA) still have an increased risk of progression and death and therefore represent an unmet medical need. Amgen and Celgene/Bristol Myers Squibb. [ABSTRACT FROM AUTHOR]