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Background: Combined therapy with carfilzomib, bendamustine, and dexamethasone was evaluated in this multicenter phase 1/2 trial conducted within the European Myeloma Network (EMN09 trial)., Methods: Sixty-three patients with relapsed/refractory multiple myeloma who had received ≥2 lines of prior therapy were included. The phase 1 portion of the study determined the maximum tolerated dose of carfilzomib with bendamustine set at 70 mg/m 2 on days 1 and 8. After 8 cycles, responding patients received maintenance therapy with carfilzomib and dexamethasone until progression., Results: On the basis of the phase 1 results, the recommended phase 2 dose for carfilzomib was 27 mg/m 2 twice weekly in weeks 1, 2, and 3. Fifty-two percent of patients achieved a partial response or better, and 32% reached a very good partial response or better. The clinical benefit rate was 93%. After a median follow-up of 21.9 months, the median progression-free survival was 11.6 months, and the median overall survival was 30.4 months. The reported grade ≥3 hematologic adverse events (AEs) were lymphopenia (29%), neutropenia (25%), and thrombocytopenia (22%). The main nonhematologic grade ≥3 AEs were pneumonia, thromboembolic events (10%), cardiac AEs (8%), and hypertension (2%)., Conclusions: In heavily pretreated patients who have relapsed/refractory multiple myeloma, combined carfilzomib, bendamustine, and dexamethasone is an effective treatment option administered in the outpatient setting. Infection prophylaxis and attention to patients with cardiovascular predisposition are required., (© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Sixty-six adult patients were treated for relapsing or refractory acute lymphocytic leukemia (ALL). The induction treatment consisted in a (1) first phase with vindesine 3 mg/m2 intravenously (IV) on days 1, 8, and 15; daunorubicin 45 mg/m2 IV on days 1, 8, and 15; erwinia-asparaginase 10,000 U/m2 IV on days 7, 8, 14, and 15; and prednisone 60 mg/m2 orally on days 1 to 21 and a (2) second phase with cytarabine 3000 mg/m2 as a 3-hour infusion two times a day on days 1 to 4 (in patients greater than 50 years of age we used 1000 mg/m2), and etoposide 100 mg/m2 IV on days 1 to 5. Side effects of induction Phase I were predominantly hematologic with subsequent infections. In Phase II, some patients additionally had gastrointestinal, cutaneous, ocular, and hepatic toxicity. Five patients died during Phase I and another died during Phase II. Five of these patients had T-cell ALL. Thirty-four (64%) of 54 patients in their first relapse had a complete remission (CR) with a median disease-free survival (DFS) of 2.9 months. The median overall survival (OAS) was 6.6 months. Seven of 12 patients with primary refractory disease, a second relapse, or relapse after bone marrow transplantation (BMT) had a CR. The CR rate and survival after first relapse was significantly better in patients with a preceding CR of more than 18 months compared with those with a shorter preceding remission. The leukocyte count was a second significant but not independent risk factor. There was a negative correlation between the leukocyte count and the duration of the preceding CR. The duration of the preceding CR was the major prognostic factor for survival in multivariate analysis. Twenty-two patients received BMT. None of nine patients with autologous BMT is alive and disease-free; 5 of 13 who underwent allogeneic BMT are. It was concluded that this treatment efficiently induced remission with tolerable toxicity. The remission duration should be improved by optimized consolidation treatment.

Lymphoid cells from two patients with hand-mirror variant of acute lymphoblastic leukemia (ALL) were studied with various monoclonal antibodies in attempts to determine their derivation and differentiation. The predominant feature of the malignant bone marrow cells was strong reactivity with antibody 3A1, which stains the majority of normal T-cells and is apparently present on all T-ALL cells. In addition, a less intense binding was observed with antibody 4F2, which reacts with activated or rapidly dividing cells, and antibody 10.2, which reacts with all thymocytes and most peripheral T-cells. Most other antibodies with a wide variety of specificities were not reactive or, in the case of a few anti-T-cell antibodies showed, by fluorescence-activated cell sorter analysis only weak staining on some cells. Sequential bone marrow studies in one patient, before and during treatment with chemotherapy, revealed a reduction of 3A1-positive cells, concordant with a decrease of malignant cells in the marrow. When involved lymph nodes, peripheral blood, or marrow were studied, similar reactivity patterns were found in all locations. The data obtained suggest that in both patients with hand-mirror variant of ALL, the malignant lymphoid cells were immature cells of early T-lymphocyte lineage. The relation of phenotype by monoclonal antibody analysis to hand-mirror morphologic type and biologic function is discussed.