Interesting new MF data from Haematologica — especially when compared with SENTRY

A phase II study of azacitidine + ruxolitinib (AZA+RUX) in myelofibrosis reported final long-term results.

Among 54 patients with chronic-phase MF:
ORR: 78%
Spleen response: 66%
Symptom response: 68%
Median OS: 56 months
Median follow-up: 95 months

The final phase II AZA + RUX study reported a 78% response rate, 66% spleen response, and 7% leukemic transformation after a median follow-up of 95.3 months. (haematologica.org⁠)

Obviously, this is a cross-trial comparison, since AZA + RUX was a single-arm phase II study.
What I find particularly interesting is the difference in the type of evidence being generated.

AZA + RUX: long-term clinical outcomes, including AML transformation.

Selinexor + RUX (SENTRY): randomized phase III evidence, with SVR35 of 49.8% vs 28.0% for RUX alone, plus an exploratory ≥20% VAF reduction in 32.0% vs 23.9% at week 24.

The VAF finding is particularly interesting because it raises the possibility that the combination may be doing more than controlling spleen volume — although it is still an exploratory endpoint and far from proving disease modification.

the really important question is:

Will longer-term SENTRY follow-up show that the VAF signal translates into lower AML transformation and/or sustain better OS?