Compassionate Use Program (CUP) with Ruxolitinib in Mexican Patients with Primary Myelofibrosis (PMF), Post – Polycythemia, Vera Myelofibrosis (PPV – MF), and Post–Essential Thrombocythemia Myelofibrosis (PET – MF)

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) that is characterized by ineffective hematopoiesis and symptomatic burden such as cytopenias, and splenomegaly. The prevalence of MF symptoms is relatively uniform across the 3 main subtypes: primary MF (PMF), post – polycythemia vera MF (PPV MF), and post – essential thrombocythemia MF (PET MF). Available therapies (AT) in Mexico, includes hydroxyurea (HU), interferon (IFN), for ET, besides phlebotomy for PV, as well as androgens, steroids, chemotherapy, IFN, thalidomide, EPO and radiotherapy for PMF. The only potentially curative therapy is allogeneic hematopoietic stem cell transplantation (HSCT) but treatment-related mortality remains high. Recently ruxolitinib an oral Janus kinase–2 inhibitor (JAK-2) has been approved to treat patients with MF. The safety and efficacy of Ruxolitinib has been evaluated 528 patients from COMFORT I and COMFORT II trials.

To report the first clinical experience in a CUP with an oral JAK–2 Inhibitor (ruxolitinib) in 40 MF patients refractory to AT in Mexico.

PMF patients and PPV/PET MF eligible for the ruxolitinib CUP, were diagnosed according to the 2008 WHO criteria, irrespective of JAK2 mutation status; classified as high risk; intermediate risk level 2; or, intermediate risk level 1 with an enlarged spleen; with a peripheral blood blast count of < 10%; adequate renal and liver function, platelet count >100×10⁹/L, all of them were treated with best available therapies in Mexico. Therapy with ruxolitinib was administered to all patients. Doses were adjusted according to the platelet counts.

Clinical and demographic characteristics were assessed at baseline and during the follow-up. The analyzed characteristics were: Demographic: age, gender; Clinical: Risk group, Bone marrow fibrosis grade, spleen size, ECOG, MPN subtype, JAK mutation, CBC counts;Spleen size at baseline and at week 20 of treatment.

The median age was 64. 2 (Interval 41 – 75). Gender distribution was 46% female and 54% male. Patients according to the International Prognostic Scoring System (IPSS) were distributed in the following risk category: 10% low risk; 53. 3% intermediate – 1 risk; 26. 7 % intermediate – 2 risk; and 20% high risk. Bone marrow fibrosis grade distribution was: Grade I 46. 15%; Grade II 23. 07%; Grade III 30. 76%. Spleen length below costal margin: <10 cm, 80. 7%; 10 to <20 cm, 11. 5% and > 20 cm, 7. 7% of patients. Spleen Average size was 9. 58 cm below costal margin at the beginning of treatment. ECOG 0 was present in 15% of patients; ECOG 1, 73%; and ECOG 2, 12% of patients. The disease subtype distribution was: PMF 45%; PPV-MF 36% and PET-MF 46%. JAK mutation was positive for 19% of patients, 46% were negative, and 35% did not have mutation analysis.

The findings from the baseline to week 20 were: Splenomegaly decreased from 9. 58 cm (avg) to 4. 5 cm (avg) (53. 02% of reduction); Median Hemoglobin level was 13. 2 gr/dL at baseline versus 10. 24 gr/dL (22. 42% of decrease). Median Platelet count was 437, 000/mm³ at baseline versus 341, 503/mm³ at week 20 of treatment (21. 85% of decrease).

Median time of treatment is 20. 1 weeks.

Hematologic adverse events presented: Hemoglobin level decrease events (CTCAE grade 2 and 3) resolved with transfusion support. Platelet count decreases (CTCAE grade 2) were transitory and resolved after two weeks of treatment interruption.

Data showed demonstrate principal characteristics of this MF cohort. Until recently, most treatments provided only palliative care with no single treatment addressing all of the complications and symptoms of the MF. Ruxolitinib showed a primary therapeutic benefit as reduction in splenomegaly and significant improvement in MF-related symptoms in this cohort of Mexican patients with myelofibrosis.

No relevant conflicts of interest to declare.