Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome.

Abstract

BACKGROUND:

After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities.

METHODS:

The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival.

RESULTS:

A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P = .004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P < .001) and a high Total Symptom Score (TSS; P < .001). During the rechallenge, 44.6% and 48.3% of the patients had spleen and symptom improvements, respectively, with a significant increase in the number of patients with a TSS reduction (P = .01). Although the use of a ruxolitinib dose > 10 mg twice daily predicted better spleen (P = .05) and symptom improvements (P = .02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P = .004).

CONCLUSIONS:

Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.

• Authors: Francesca Palandri, Mario Tiribelli, Massimo Breccia, Daniela Bartoletti, Elena M Elli, Giulia Benevolo, Bruno Martino, Francesco Cavazzini, Alessia Tieghi, Alessandra Iurlo, Elisabetta Abruzzese, Novella Pugliese, Gianni Binotto, Giovanni Caocci, Giuseppe Auteri, Daniele Cattaneo, Malgorzata M Trawinska, Rossella Stella, Luigi Scaffidi, Nicola Polverelli, Giorgia Micucci, Elena Masselli, Monica Crugnola, Costanza Bosi, Florian H Heidel, Roberto Latagliata, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M Lemoli, Michele Cavo, Nicola Vianelli, Massimiliano Bonifacio, Giuseppe A Palumbo
• Journal: Cancer (Cancer) Vol. 127 Issue 15 Pg. 2657-2665 (08 01 2021) ISSN: 1097-0142 [Electronic] United States
• PMID: 33794557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 American Cancer Society.

Chemical References

• Nitriles
• Pyrazoles
• Pyrimidines
• ruxolitinib

Topics

• Humans
• Nitriles
• Primary Myelofibrosis (drug therapy)
• Pyrazoles
• Pyrimidines (therapeutic use)
• Retrospective Studies
• Treatment Outcome