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Ruxolitinib therapy appears safe prior to allogeneic HSCT for myelofibrosis

Rachel B. Salit
Photo credit: Fred Hutchinson
Cancer Research Center

SALT LAKE CITY — Ruxolitinib treatment prior to allogeneic hematopoietic stem cell transplant appeared safe and aided in the prevention of cytokine release syndrome among patients with myelofibrosis, according to results of a phase 2 prospective study presented at the BMT Tandem Meetings.

“[The implications of the study] will let us know if patients with myelofibrosis who take ruxolitinib prior to undergoing stem cell transplant have better posttransplant outcomes,” Rachel B. Salit, MD, assistant member in the clinical research division at Fred Hutchinson Cancer Research Center and physician at Seattle Care Cancer Alliance, told HemOnc Today. “Almost all patients are starting ruxolitinib for myelofibrosis now and they are delaying transplant. There is likely an optimal time for them to move forward when they would do much better in terms of relapse and nonrelapse mortality.”

Allogeneic HSCT is the only potential cure for myelofibrosis; however, guidelines suggest the risk for transplant-related complications are acceptable only for transplant-eligible patients with intermediate-2 or high-risk disease based on the dynamic international predictive scoring system.

Salit and colleagues hypothesized the use of ruxolitinib (Jakafi, Incyte) — a JAK inhibitor — pretransplant would decrease dynamic international predictive scoring system score, improve constitutional symptoms and reduce splenomegaly, thus improving post-HSCT survival.

The two-part trial included 28 patients (median age, 56 years) with primary (n = 15) or secondary (n = 13) myelofibrosis who received ruxolitinib for a minimum of 8 weeks (median, 7.5 months; range, 2-30) prior to HSCT.

“We did not limit the duration of the JAK inhibitor; it just had to be at least 8 weeks and patients were monitored in their own oncology office,” Salit said during her presentation. “Providers were directed to check labs every 4 weeks and see patients monthly.”

In part two of the study, patients consented for transplant and ruxolitinib treatment tapered over 1 to 2 weeks through day 4 of conditioning. Patients received conditioning per provider choice with 120 mg/m2 fludarabine and 140 mg/m2 melphalan (n = 3) or 120 mg/kg cyclophosphamide and 16 mg/kg busulfan (n = 19).

Prior to JAK inhibitor treatment, one patient was deemed low risk, seven were intermediate-1 risk and 14 patients were intermediate-2 risk.

Donor sources included 14 related, five unrelated and three double cord blood grafts. Patients who underwent transplant with cord blood received 75 mg/m2 fludarabine in addition to cyclophosphamide/busulfan conditioning.

Two-year posttransplant survival served as the primary endpoint. Secondary endpoints included graft failure, 1-year relapse and incidence of graft-versus-host disease.

Median follow-up was 12.5 months (range, 1.6-35.7). All patients were engrafted at a median of 19 days (range 14-35). No graft failures were reported and no incidences of cytokine release syndrome occurred.

The median chimerism at day 80 was 88% for CD3 and 100% for CD33.

Researchers observed chronic GVHD among six of 17 evaluable patients, with two cases being severe. Incidence of acute GVHD at grade 2 to grade 4 was 70%, and at grade 3 to grade 4 was 15%.

Two patients relapsed; one relapsed at 6 months with marrow blasts and another patient at 2 years with myeloid sarcoma.

The 1-year survival rate was 93% (95% CI, 0.73-0.98) and 2-year survival was 86% (95% CI, 0.61-0.96). In comparison, 1-year survival in historical controls was 54%.

Although results are promising, the low number of patients created a limitation within the study.

“The numbers are small, but that will always be the case for a rare disease like myelofibrosis,” Salit said.

Overlapping a JAK inhibitor with conditioning chemotherapy was safe and prevented cytokine release syndrome. However, more research is needed.

“We don’t know the optimal time on ruxolitinib, after which a patient should move forward with transplant,” Salit told HemOnc Today. “We also don’t know if it is safe to continue it through transplant.” – by Melinda Stevens

 

Reference:

Salit RB, et al. Abstract 17. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.

 

Disclosures: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of reporting.

Rachel B. Salit
Photo credit: Fred Hutchinson
Cancer Research Center

SALT LAKE CITY — Ruxolitinib treatment prior to allogeneic hematopoietic stem cell transplant appeared safe and aided in the prevention of cytokine release syndrome among patients with myelofibrosis, according to results of a phase 2 prospective study presented at the BMT Tandem Meetings.

“[The implications of the study] will let us know if patients with myelofibrosis who take ruxolitinib prior to undergoing stem cell transplant have better posttransplant outcomes,” Rachel B. Salit, MD, assistant member in the clinical research division at Fred Hutchinson Cancer Research Center and physician at Seattle Care Cancer Alliance, told HemOnc Today. “Almost all patients are starting ruxolitinib for myelofibrosis now and they are delaying transplant. There is likely an optimal time for them to move forward when they would do much better in terms of relapse and nonrelapse mortality.”

Allogeneic HSCT is the only potential cure for myelofibrosis; however, guidelines suggest the risk for transplant-related complications are acceptable only for transplant-eligible patients with intermediate-2 or high-risk disease based on the dynamic international predictive scoring system.

Salit and colleagues hypothesized the use of ruxolitinib (Jakafi, Incyte) — a JAK inhibitor — pretransplant would decrease dynamic international predictive scoring system score, improve constitutional symptoms and reduce splenomegaly, thus improving post-HSCT survival.

The two-part trial included 28 patients (median age, 56 years) with primary (n = 15) or secondary (n = 13) myelofibrosis who received ruxolitinib for a minimum of 8 weeks (median, 7.5 months; range, 2-30) prior to HSCT.

“We did not limit the duration of the JAK inhibitor; it just had to be at least 8 weeks and patients were monitored in their own oncology office,” Salit said during her presentation. “Providers were directed to check labs every 4 weeks and see patients monthly.”

In part two of the study, patients consented for transplant and ruxolitinib treatment tapered over 1 to 2 weeks through day 4 of conditioning. Patients received conditioning per provider choice with 120 mg/m2 fludarabine and 140 mg/m2 melphalan (n = 3) or 120 mg/kg cyclophosphamide and 16 mg/kg busulfan (n = 19).

Prior to JAK inhibitor treatment, one patient was deemed low risk, seven were intermediate-1 risk and 14 patients were intermediate-2 risk.

Donor sources included 14 related, five unrelated and three double cord blood grafts. Patients who underwent transplant with cord blood received 75 mg/m2 fludarabine in addition to cyclophosphamide/busulfan conditioning.

Two-year posttransplant survival served as the primary endpoint. Secondary endpoints included graft failure, 1-year relapse and incidence of graft-versus-host disease.

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Median follow-up was 12.5 months (range, 1.6-35.7). All patients were engrafted at a median of 19 days (range 14-35). No graft failures were reported and no incidences of cytokine release syndrome occurred.

The median chimerism at day 80 was 88% for CD3 and 100% for CD33.

Researchers observed chronic GVHD among six of 17 evaluable patients, with two cases being severe. Incidence of acute GVHD at grade 2 to grade 4 was 70%, and at grade 3 to grade 4 was 15%.

Two patients relapsed; one relapsed at 6 months with marrow blasts and another patient at 2 years with myeloid sarcoma.

The 1-year survival rate was 93% (95% CI, 0.73-0.98) and 2-year survival was 86% (95% CI, 0.61-0.96). In comparison, 1-year survival in historical controls was 54%.

Although results are promising, the low number of patients created a limitation within the study.

“The numbers are small, but that will always be the case for a rare disease like myelofibrosis,” Salit said.

Overlapping a JAK inhibitor with conditioning chemotherapy was safe and prevented cytokine release syndrome. However, more research is needed.

“We don’t know the optimal time on ruxolitinib, after which a patient should move forward with transplant,” Salit told HemOnc Today. “We also don’t know if it is safe to continue it through transplant.” – by Melinda Stevens

 

Reference:

Salit RB, et al. Abstract 17. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.

 

Disclosures: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of reporting.

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