Evgeni Chubar

Efficacy and safety of salvage therapy using Carfilzomib for relapsed or refractory multiple myeloma patients: a multicentre retrospective observational study

Carfilzomib has been established in previous years as a treatment for patients with relapsed and/or refractory multiple myeloma (RR‐MM). A retrospective multicentre study to evaluate the clinical use of carfilzomib for RR‐MM outside of a clinical trial setting was conducted by our group. One hundred and thirty‐five patients were included. All patients had been previously exposed to bortezomib and 93% had also been treated with lenalidomide. The vast majority of patients received carfilzomib as part of a two‐ or three‐drug combination. The overall response rate was 47·2%. Multivariate analysis revealed bortezomib resistance, lenalidomide resistance and albumin <35 g/l to negatively impact the likelihood of achieving response. The median duration of response was 8·4 months, and was significantly higher in patients receiving three‐drug combination and patients presenting without extramedullary disease. The median progression‐free survival and overall survival for the entire cohort was 4·9 months (95% confidence interval [CI] 3·8–6·4) and 12·2 months (95% CI 9‐not reached), respectively. Toxicity was manageable, although treatment‐related death was seen in 5% of patients. In the setting of progressive multiple myeloma, carfilzomib in a combination regimens yields effective results with a manageable toxicity.

Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice

Ruxolitinib has been shown in two randomized clinical trials to be effective in alleviating systemic symptoms and reducing spleen size in patients with myelofibrosis (MF). We retrospectively evaluated efficacy and tolerability of ruxolitinib in a cohort of unselected MF patients treated in routine clinical practice. One hundred and two patients who began ruxolitinib therapy were identified in 13 participating centers. Ninety three of the patients receiving ruxolitinib for at least 3 months were evaluated for treatment efficacy and toxicity. Median age at ruxolitinib initiation was 67 years. Indications for treatment were constitutional symptoms (15%), symptomatic splenomegaly (6%) or both (76%). Two patients received ruxolitinib for other indications. The median initial ruxolitinib dose was 30mg/day. Median duration of therapy was 11 months. Eighty two patients (88.2%) responded to therapy, 76 (84.4%) patients had improvement in constitutional symptoms and 60 patients (70.6%) had reduction in spleen length. While on ruxolitinib, 30% of patients had grade 3-4 anemia and 12.9% of patients had grade 3-4 thrombocytopenia. Thirteen patients (14%) discontinued therapy. This analysis of a cohort of MF patients treated with ruxolitinib in routine clinical practice demonstrates the efficacy and tolerability of this drug outside of a highly monitored clinical trial setting.

Outcomes of light-chain amyloidosis patients treated with first-line bortezomib: a collaborative retrospective multicenter assessment.

Light‐chain amyloidosis (AL) is associated with low survival rates, particularly in patients with cardiac involvement. We evaluated the outcome of 73 consecutive, non‐selected ‘real‐world’ AL patients, treated with first‐line bortezomib‐based induction, focusing on the benefit of concurrent administration of alkylating agents. Most patients had renal (77%), cardiac (66%), or multiorgan (74%) involvement. Sixty‐eight per cent (n = 50) received alkylating agent (mostly cyclophosphamide). Severe adverse events were seen in 45%, most evident in patients with cardiac involvement, with no increased toxicity in patients receiving an alkylator agent. Hematological response (HemR) was obtained in 77% of patients, including 33% very good partial responses and 19% complete responses. Age <70 yr, lack of cardiac and peripheral neurologic involvement, and co‐administration of an alkylating agent were associated with significantly improved HemR. NYHA cardiac failure staging was the only independent factor affecting overall survival. Administration of an alkylating agent and the achievement of both HemR and organ response were associated with a statistically significant improved survival in those surviving the first 6 months of induction. First‐line bortezomib‐based regimen resulted in favorable response and survival in newly diagnosed patients. Co‐administration of an alkylating agent improved outcome without increasing treatment‐related toxicity.

Real-life Experience With Ponatinib in Chronic Myeloid Leukemia: A Multicenter Observational Study

Background: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). Patients and Methods: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. Results: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase. Only 9 patients (26%) harbored the T315I (threonine to isoleucine mutation at position 315) mutation. All patients had received ≥ 1 previous tyrosine kinase inhibitor. The median age in our cohort was 43 years (range, 9–82 years), significantly younger than expected for patients with relapsed or refractory CML and 20 years younger than the median age of patients who participated in the PACE (ponatinib Philadelphia‐positive acute lymphoblastic leukemia and CML evaluation) trial. During a median follow‐up of 14 months (range, 1–51 months), the overall response rate was 85%. Of 34 patients, 16 (47%) experienced at least a major molecular response. Of the 37 total patients, another 16 patients (43%) discontinued treatment because of disease progression (n = 6), vascular complications (n = 1), severe cytopenia (n = 2), or for other reasons (n = 7). Conclusion: In real life, ponatinib is a “niche‐drug” reserved for a unique population of exceptionally young patients with CML with or without the T315I mutation. In this highly selected group, very different from the PACE cohort, ponatinib achieved high overall response rates. Micro‐Abstract In the present study, we identified 37 patients with chronic myeloid leukemia in 7 medical centers to study how ponatinib is used outside of clinical trials. At least 1 previous tyrosine kinase inhibitor had failed in all 37 patients. Their median age was 43 years (range, 9–82 years), and the overall response rate was 85%. Outside of clinical trials, ponatinib has been reserved for exceptionally young patients; however, responses can be expected even in heavily pretreated patients.

Fatal delayed haemolytic transfusion reaction in a patient without previous transfusions but with an obstetric history of 13 pregnancies

Delayed haemolytic transfusion reaction is a rare, life-threatening complication of blood transfusion that has been typically described among patients with sickle cell disease (SCD) due to alloimmunisation induced by their exposure to red blood cell antigens through recurrent transfusions. We report the case of a patient who suffered from fatal delayed haemolytic transfusion reaction (DHTR) occurring 1 week after blood transfusion. Indirect antiglobulin testing confirmed the presence of anti-Kell antibodies that were absent in the pretransfusion sample. The patient did not receive blood transfusions in the past, but her obstetric history was remarkable for 13 pregnancies. Although DHTR occurs more commonly among patients with SCD, this type of reaction can occur in any patient who is able to mount an immune response. We would to like to draw the attention of physicians to this rare and potentially lethal complication of blood transfusion, especially in grand multiparous women.