Page 112 - Haematologica-5

E. Van Den Neste et al.
control of pruritus, which affected 35.5% of patients prior to initiating therapy but only 6.6% after the first cycle of ruxolitinib. Sweating, which was present in 32.2% of the patients at inclusion, was reduced, with 20% still having this symptom after one cycle of treatment. Fever was abolished in 3/4 patients with this symptom at inclusion.
The median follow-up was 17.5 months. As illustrated in Figure 5, the median progression-free survival was 3.5 months (95% CI: 1.9-4.6). The median duration of response was 7.7 months (95% CI: 1.8-NA) for the six patients who eventually a achieved response (data not shown). Overall, 30 patients had progressive disease, with 97% at the initial site and/or 60% at new sites. Following ruxolitinib discontinuation, 25 (83.3%) patients were given further treatments, consisting of chemotherapy in 19, and immunotherapy in nine, the latter comprising rit- uximab in four, BV in three, and nivolumab in two. Transplantation was eventually carried out in five patients, and was allogeneic in four cases and autologous in the remaining one. Among the 25 patients prescribed further therapy, the observed complete and partial response rates were 10% and 15%, respectively. Overall, 12 patients died on account of lymphoma progression (83.3%), toxicity of other treatments (8.3%), or other rea- sons (8.3%). The median overall survival was 27.1 months (95% CI: 14.4-27.1).
A
B
Figure 2. Response after ruxolitinib. Illustrative patient (UPN 601004). (A) Positron emission tomography (PET)-computer tomography (CT) frontal view. (B) PET-CT sagittal view. Partial response with allievation of B symptoms and blood inflammation was achieved 2 months after starting ruxolitinib. At month 6, the patient had slowly progressive disease but refused to stop ruxolitinib. CRP: C- reactive protein.
Safety
All patients enrolled in the study received at least one dose of study medication and were, therefore, included in the safety analysis. Overall, 40 adverse events were observed in 14/33 patients (42.4%). In six patients, the adverse events were related to the ruxolitinib therapy. In eight of them, the events were of grade ≥3 (Table 4A). Among the 40 adverse events recorded, 30 (75%) occurred during induction and 18 (45%) were related to ruxolitinib. No drug-related deaths were recorded. One adverse event resulted in permanent drug discontinuation, while 87.5% of the adverse events resolved without sequelae. The characteristics and grade of the adverse events, listed by system organ class and preferred terms, are displayed in Table 4B. Twenty-five (62.5%) were of grade ≥3. These were mostly anemia (n=11), all considered related to rux- olitinib. Other main causes of grade ≥3 adverse events included lymphopenia (n=4), infections (n=3) and miscel- laneous causes. Of note, no cases of grade 4 neutropenia or thrombocytopenia were observed.
Eight serious adverse events were reported in four patients, during induction (n=5), maintenance (n=1) or after the end of treatment (n=2). These serious adverse events consisted of infection in three patients (device- related sepsis, gastroenteritis, and lung infection). The other serious adverse events were anemia, diarrhea, sub- dural hematoma, bone pain, and pulmonary embolism. Two serious adverse events (anemia, lung infection) were deemed drug-related and six were considered grade ≥3: infection (n=3), anemia, subdural hematoma, and pul- monary embolism. Of the eight serious adverse events, six resolved without sequelae, while the device-related sepsis and pulmonary embolism, observed in the same patient, persisted until the patient died due to progressive disease and were thus not considered as the cause of death. Among the 33 patients, one second primary malignancy was observed (adenocarcinoma of the colon in an 80-year old male patient).
Biomarker analysis
Using bead-based immunoassays, plasma levels of 27 cytokines related to the immune system were measured at
Figure 3. Response after ruxolitinib. Illustrative patient (UPN 601001). Comparison of frontal positron emission tomography (PET)-scan prior to inclu- sion and after 2 months of ruxolitinib. There was a rapid improvement of con- stitutional symptoms after a few days on ruxolitinib. PET after 2 months showed metabolic partial response with a total volume reduction of tumor lung lesions of 64%.
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haematologica | 2018; 103(5)