Details

Autor(en) / Beteiligte

• Verstovsek, Srdan
• Kiladjian, Jean‐Jacques
• Vannucchi, Alessandro M.
• Mesa, Ruben A.
• Squier, Peg
• Hamer‐Maansson, J. E.
• Harrison, Claire

Titel

Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT‐I and COMFORT‐II studies

Ist Teil von

• Cancer, 2023-06, Vol.129 (11), p.1681-1690

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Background In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT‐I) and COMFORT‐II clinical trials, adult patients with intermediate‐2 or high‐risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS). Methods This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation. Results The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT. Conclusions These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate‐2 and high‐risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS. Plain Language Summary Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue. Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments. Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment. Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed. A pooled analysis of the Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT‐I) and COMFORT‐II phase 3 trials suggests that earlier ruxolitinib initiation in adult patients with intermediate‐2 or high‐risk myelofibrosis is associated with improved clinical outcomes, including significantly prolonged overall survival and improved spleen and symptom responses. These data suggest that patients with myelofibrosis may benefit from earlier intervention.