The purine nucleoside analogues cladribine and pentostatin are highly-active first-line therapeutic treatments for hairy cell leukemia (HCL), resulting in complete response rates of 80 to 90%. However, HCL patients continue to relapse, and sooner or later, most require subsequent lines of treatment. This report presents the relapsed patients with classic HCL who were treated with vemurafenib (mostly at the low dose of 240 mg twice daily for 16 weeks) combined with rituximab after the failure of several lines of therapy including cladribine with or without rituximab and moxetumomab pasudotox. Two patients achieved CR MRD (-) after combined treatment with vemurafenib and rituximab, with a hematologic response ongoing after 38 months from the end of treatment in one patient and a relapse of cytopenias occurring after 13 months in the other patient. A third patient normalized her blood counts and this hematologic response, which was not evaluated in the bone marrow at the end of treatment, was lost after 18 months. The last patient died due to infection and multi-organ failure, too early to verify response to vemurafenib. Two patients who had relapsed after vemurafenib and rituximab derived meaningful clinical benefit from retreatment with the same agents, but eventually relapsed again and started indefinite therapy with dabrafenib and trametinib with normalization of the blood counts despite heavy bone marrow infiltration in the only patient so far evaluable. The outcomes of these cases indicate that novel targeted agents, and in particular vemurafenib combined with rituximab, improve the prognosis of HCL patients, even those heavily pretreated with PNAs and moxetumomab pasudotox

Fragility scales are intended to help in therapeutic decisions. Here we asked if the fragility as-sessment in MM patients ≥75 years old qualified for treatment by the local physician correlates with the choice of treatment: a 2- or 3-drug regimen. Between 7/2018 to 12/2019 we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in com-pletely dependent. Patients with more than 3 comorbidities were 26.9% (53 patients). Thus, ac-cording to the Palumbo calculator, 43 patients were in the intermediate-fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received 3-drug regimens and 20.3% (40) received 2-drug regimens. In each ECOG group, more than 3/4 of patients received 3-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received 3-drug regimens. Out of 53 pa-tients with at least 4 comorbidities, 71.7% received 3-drug regimens, and the rest 2-drug regi-mens. Three-drugs regimens received 34 patients from the intermediate-fit group (79.0%), and 123 (79.9%) from the frail group. Early mortality occurred in 25 patients (12.7%). No one discon-tinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with tri-ple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations which questions the clinical utility of current fragility scales in everyday practice.