In today's NEJM, there is a letter reflecting a "sponsor-independent analysis" that posts a somewhat grim picture of the long-term results with ruxolitinib:
According to conventional criteria, response rates were 29% for spleen, 21% for anemia, 63% for constitutional symptoms, and 92% for pruritus. Side effects included grade 2 or higher thrombocytopenia (in 26% of patients) and anemia (in 33% of patients).
Treatment has so far been discontinued in 47 patients (92%). Rates of treatment discontinuation at 1, 2, and 3 years were 51%, 72%, and 89%, respectively. Reasons for treatment discontinuation included disease progression or loss or lack of response (40%) and toxicity with or without disease progression or lack of response (34%). During drug discontinuation, serious adverse events that necessitated hospitalization occurred in at least 5 patients (11%) and constituted acute relapse of symptoms, rapid and painful enlargement of the spleen, and acute hemodynamic decompensation, which occasionally led to a septic shock–like syndrome.
To date, 18 patients (35%) have died, and 5 patients (10%) have had leukemic transformations. There was no significant difference in the survival rate for the 51 ruxolitinib-treated patients, as compared with a cohort of 410 patients with primary myelofibrosis who were treated with standard therapy at the Mayo Clinic in the most recent 10-year period (P=0.43 without adjustment; P=0.58 with adjustment for the DIPSS Plus score)
We conclude that ruxolitinib is effective in alleviating constitutional symptoms in the majority of patients with myelofibrosis. Its activity in reducing spleen size is modest and not always durable. It is imperative that patients be alerted about important drug adverse events, including thrombocytopenia, worsening of anemia, and serious withdrawal symptoms.
I'm out of the stock on this update.
Peter |
