Background
Compared with older 5‐HT3 receptor antagonists, palonosetron requires fewer drug administrations to prevent chemotherapy‐induced nausea and vomiting (CINV) following multiple‐day ...chemotherapy. We conducted a phase II multicenter study comparing palonosetron plus aprepitant to palonosetron alone in patients undergoing a range of induction chemotherapy regimens for acute myeloid leukemia (AML).
Methods
Patients were randomized to palonosetron (0.25 mg) every other day until the last dose of chemotherapy alone or with aprepitant on days 1‐3. Patients mainly received an anthracycline on days 1‐3 plus cytarabine administered for 5‐10 days. The primary end point was complete response (CR; no emesis and no rescue medication) over the whole study period (days of chemotherapy plus two additional days). Unplanned analysis of time to anti‐emetic treatment failure (TTF) was also performed.
Results
Of the 134 patients enrolled in the study, 130 were evaluable: 68 subjects received palonosetron plus aprepitant and 62 received palonosetron alone. Although the primary end point of CR was similar between the treatment arms (72% vs 69%; P = .55), a higher proportion of patients treated with palonosetron plus aprepitant were free from nausea during the whole study period (43% vs 27%; P = .03). There was also a significant difference in favor of the two‐drug regimens in TTF (median: 5 days vs 3 days; P = .03).
Conclusions
The study suggests that every‐other‐day palonosetron plus 3‐day aprepitant can add clinical benefit to the control of CINV caused by multiple‐day, corticosteroid‐free chemotherapy for AML. In this challenging setting of CINV, further investigations of palonosetron in combination with aprepitant administered with an expanded schedule are warranted.
ClinicalTrial.gov identifier: NCT02205164.
In this randomized study on acute myeloid leukemia patients treated with multiple‐day induction chemotherapy, the authors investigated the efficacy of a simplified antiemetic prophylaxis consisting of every‐other‐day palonosetron plus 3‐day aprepitant compared to palonosetron alone. Although similar rates of complete response were observed, the combination regimen significantly improved control of nausea in this challenging setting of chemotherapy‐induced nausea and vomiting.
The ASPIRE (NCT01080391) phase 3 trial showed the efficacy of carfilzomib, lenalidomide and dexamethasone (KRd) triplet for relapse and refractory multiple myeloma (RRMM). However, little is known ...about safety and efficacy of KRd outside a clinical trial context.
Herein we report real life results of KRd given to 130 RRMM patients from 12 Sicilian Centers.
Median age was 62 years; patients had received a median of two previous lines of treatment (range 1-10) and 52% were refractory to previous treatment. Median number of KRd cycles was 12 (2-29), with a mean duration of treatment of 12 months; 21 patients had received at least 18 cycles. Overall response rate was 61%, including 18% complete response. Median PFS was 22.9 months, median OS was not reached. Creatinine clearance >30 mL/min, quality of the best achieved response and standard Fluorescence In Situ Hybridization (FISH) risk were independent predictors of favorable outcome. Patients who received the full-dosage of carfilzomib in the first two cycles had a better outcome.
KRd was effective and well tolerated and in a considerable proportion of patients, therapy continued beyond the 18th cycle. The finding of a better outcome in patients with the higher cumulative dose of carfilzomib in the first two cycle encourages to maintain the maximum tolerated dose.
Summary
High‐dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable ...proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third‐generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR‐HL accrued into a prospective registry‐based study. Application of FEAM resulted in a 2‐year progression‐free survival (PFS) of 73·8% 95% confidence interval (CI), 0·64–0·81 with median PFS, overall survival and time to progression yet to be reached. The 2‐year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12–0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose (18FFDG)‐uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had 18FFDG‐positrin emission tomography‐positive lesions before HDT, the 2‐year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12–0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR‐HL patients typically pre‐exposed to lung‐damaging treatments.
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