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Home > Efficacy

Start JAKAVI earlier for superior survival outcomes[1]

COMFORT II: Overall survival by treatment initiation timing[1]

5.3 years with immediate Jakavi treatment from COMFORT II

Immediate initiation of JAKAVI treatment improved overall survival by 33%

  • In a pooled analysis of the pivotal trials, earlier initiation of treatment with JAKAVI resulted in greater reduction in risk of death vs delayed JAKAVI initiation[2]*
OS, overall survival; RPSFT, rank-preserving structural failure time.
*After adjusting for crossover by using a RPSFT model, reduction in risk of death was greater in patients who were originally randomised to JAKAVI compared with patients who crossed over (HR [JAKAVI vs RPSFT]=0.35; 95% CI, 0.23-0.59).

 

In 2 pivotal trials of 528 patients, JAKAVI significantly extended survival vs BAT, including HU[3]

Pooled COMFORT-I and COMFORT-II: 5-year follow-up

65% reduction in risk of death with JAKAVI. Pooled COMFORT-1 and COMFORT-II: 5-year follow-up

According to ELN Guidelines, the primary goal of treatment is extending overall survival for patients ineligible for stem-cell transplant[4]

COMFORT-I

  • At 1-year follow-up (median: 51 weeks), JAKAVI demonstrated survival improvement (HR=0.50; 95% CI, 0.25-0.98; P=0.04)[5]

COMFORT-II

  • At 3.5 years, JAKAVI treatment was associated with a 42% reduction in risk of death vs BAT (HR=0.58; 95% CI, 0.36-0.93; P=0.02)[6]
  • At 5-year follow-up, there was a 33% reduction in risk of death with JAKAVI compared with BAT by ITT analysis (HR=0.67; 95% CI, 0.44-1.02; P=0.06)[1]
BAT, best available therapy; COMFORT, Controlled Myelofibrosis Study with Oral JAK Inhibitor Therapy; ELN, European LeukemiaNet; HU, hydroxyurea; ITT, intent-to-treat.
†Results from an exploratory analysis of pooled data from 528 patients in the COMFORT-I and COMFORT-II trials. Seventy percent of patients in the control group crossed over to JAKAVI during the study. The control group in COMFORT-I received placebo. The control group in COMFORT-II received BAT; the three most common were HU (47%), no medication (33%), and prednisone/prednisolone (12%). The crossover-corrected treatment effect was estimated using an RPSFT method and through censorship of survival time at the time of crossover.

 

Start JAKAVI earlier for superior spleen response[7]

Early intervention with JAKAVI increased the probability of spleen response by almost 60%[7]

Predictors of spleen response with JAKAVI

Spleen response with Jakavi increased by almost 60% chart

 

Results from a study of 70 intermediate-1 IPSS risk MF patients treated with JAKAVI in 15 Italian (and 1 German) haematology centers. Patients received JAKAVI based on physician’s discretion after inclusion in the JUMP trial (n=51) or within a compassionate use program (n=19) and were evaluated for responses according to 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.

Regression logistic analysis was performed to correlate spleen/symptoms responses with several baseline features, namely sex, primary/secondary MF,  age >65 years, transfusion dependency, leukocytosis (>25x109/L), presence of constitutional symptoms and blast cells, palpable hepatomegaly, JAK2V617F mutation and mutation load, severe (grade 3) marrow fibrosis, Charlson Comorbidity Index ≥2, overweight, large splenomegaly (spleen length palpable ≥10 and ≥15 cm below left coast margin), TSS higher than the median value (≥20) and severely increased (≥44).

Rapid, durable spleen reduction for superior survival vs BAT (including HU)[8]

COMFORT II: Mean percentage change in spleen volume

Spleen response with Jakavi increased by almost 60% chart

Each 10% reduction in spleen length from baseline was associated with a 9% reduction in risk of death[8]

  • 97% of patients treated with JAKAVI achieved spleen reduction at any point in the study while BAT-treated patients progressively worsened[1]
  • JAKAVI delivered spleen reductions as early as Week 12, with results sustained over time, regardless of JAK2V617F mutational status[9]
BAT, best available treatment.

 

Earlier treatment with JAKAVI increased the probability of symptom response by 54%[7]

Predictors of symptom response with JAKAVI

Predictors of symptom response with Jakavi chart

JAKAVI demonstrated superior symptom improvement compared with BAT (including HU)[9]

COMFORT-II: Mean change in EORTC QLQ-C30 symptom scores

Mean change in EORTC QLQ-C30 symptom scores chart from COMFORT-II

JAKAVI improves patients’ symptoms rapidly and durably[5]

COMFORT-I: Proportion of patients with ≥50% reduction in TSS over time

Symptom reduction in TSS over time chart from COMFORT-I

JAKAVI has a predictable pharmacodynamic profile with steady haemoglobin and platelet levels sustained over time

Treatment resulted in an expected and manageable decrease in haemoglobin and platelet levels, although to a lesser degree with JAKAVI vs BAT[10]

COMFORT II: Haemoglobin levels over time

Haemoglobin levels over time chart from COMFORT-II

 

COMFORT II: Platelet counts over time

Platelet counts over time chart from COMFORT-II

 

  • Mean decreases in haemoglobin reached a nadir of approximately 10 g/L below baseline after 8 to 12 weeks of therapy and then gradually recovered to reach a new steady state that was approximately 5 g/L below baseline[10],[11]
  • Thrombocytopenia typically presented within the first 8 weeks of therapy and was manageable with temporary dose reduction or interruption[11]

JAKAVI provided consistent overall survival benefits in patients with and without anaemia

Pooled COMFORT-I and COMFORT-II: No anaemia at baseline[12]

Pooled COMFORT-I and COMFORT-II: No anaemia at baseline chart

 

Pooled COMFORT-I and COMFORT-II: Anaemia at baseline[12]

Pooled COMFORT-I and COMFORT-II: Anaemia at baseline chart

 

  • Regardless of baseline Hb levels, new or worsening anaemia that occurred during JAKAVI treatment had no effect on OS[12]
BAT, best available therapy; HU, hydroxyurea; OS, overall survival.
*After Week 144, the interpretation of the curves is affected by low numbers of patients.

References

  1. Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30(8):1701-1707.

  2. Verstovsek S, Gotlib J, Mesa RA, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017;10(1):156.

  3. Verstovsek S, Gupta V, Gotlib JR, et al. A pooled overall survival (OS) analysis of 5-year data from the COMFORT-I and COMFORT-II trials of ruxolitinib for the treatment of myelofibrosis (MF). Blood. 2016;128(22):3110.

  4. Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761-770.

  5. Verstovsek S, Mesa RA, Gotlib J, et al. Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2013;98(12):1865-1871.

  6. Harrison C, Niederwieser D, Vannuchi A, et al. Results from a 3.5 year update of COMFORT-II, a phase 3 study comparing ruxolitinib (RUX) with best available therapy (BAT) for the treatment of myelofibrosis. Abstract presented at: 19th Congress of the European Hematology Association; June 12-15, 2014; Milan, Italy.

  7. Palandri F, Palumbo GA, Bonifacio M, et al. Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis. Oncotarget. 2017;8(45):79073-79086.

  8. Vannucchi AM, Kantarjian HM, Kiladjian J-J, et al. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015;100(9):1139-1145.

  9. Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-798.

  10. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113(13):2895-2901.

  11. JAKAVI® (ruxolitinib) tablets: EU Summary of Product Characteristics. Novartis; August 2021.

  12. Gupta V, Harrison C, Hexner EO, et al. The impact of anemia on overall survival in patients with myelofibrosis treated with ruxolitinib in the COMFORT studies. Haematologica. 2016;101(12):e482-e484.