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SALT LAKE CITY – The use of Janus kinase (JAK) inhibitor therapy prior to hematopoietic stem cell transplantation is safe and may improve posttransplant survival in patients with myelofibrosis, according to findings from an ongoing prospective phase 2 study.
The 1-year overall survival rate among the 28 initial patients in the single-center study of JAK inhibitor therapy followed by myeloablative or reduced-intensity hematopoietic cell transplantation (HCT) was 93%. The 2-year survival rate was 89%, compared with 54% in a closely matched historical cohort of intermediate-2–risk patients who did not receive pre-HCT JAK inhibitor therapy, Rachel B. Salit, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
“So this is pretty exciting for us,” she added, explaining that allogeneic HCT, which is currently indicated only for patients with intermediate-2– or high-risk disease on the Dynamic International Prognostic Scoring System (DIPSS), remains the only curative treatment option for patients with myelofibrosis.
“Transplant outcomes have been associated with DIPSS and DIPSS+ risk scores,” she said, adding that a study demonstrating that association showed a 54% survival rate at 3 years in patients with intermediate-2–risk disease. “Then JAK-2 inhibitors came down the pipe, and they are also indicated for patients with DIPSS intermediate-2– and high-risk disease. They’ve been shown to decrease spleen size, increase quality of life scores, decrease cytokine levels, and improve constitutional symptoms.”
Posttransplant benefits of pre-HCT JAK inhibitor therapy could include improved graft function because of decreased spleen size and cytokines, potentially decreased severe graft-versus-host disease (GVHD), and decreased nonrelapse mortality.
“Our hypothesis was that the use of JAK inhibitors before transplant in patients with myelofibrosis – by decreasing inflammation, improving constitutional symptoms, and reducing splenomegaly – would result in a decreased DIPSS score” and improved posttransplant survival, Dr. Salit said.
Study participants were patients aged 18 years and older (median of 53 years) with primary or secondary myelofibrosis (14 each). About two-thirds of the study participants were men. Prior to JAK inhibitor therapy, 2 patients were low risk, 10 patients were intermediate-1 risk, and 16 patients were intermediate-2 risk according to the DIPSS.
They were given ruxolitinib (Jakafi) for at least 8 weeks prior to HCT (median of 7 months, but up to 3 years), and the treatment was tapered over 1-2 weeks through day 2 or 3 of conditioning chemotherapy, depending on the conditioning regimen. Conditioning regimens were determined by the physician based on donor type.
“After the ruxolitinib, we had 6 patients who were intermediate-1 and 21 who were intermediate-2, so in that way they failed to meet that hypothesis,” Dr. Salit said. This happened because the patients became anemic, so they gained points on their DIPSS scores for declining constitutional symptoms.
Of the 28 participants, 23 received myeloablative HCT, and 5 received reduced-intensity HCT.
“We had a mixture of related, unrelated, and cord blood recipients,” she noted.
At a median follow-up of just over 1 year, and at up to 3 years in some patients, no cases of cytokine release syndrome have occurred with the overlap of ruxolitinib and conditioning chemotherapy, and there have been no graft failures. All patients, including cord blood recipients, engrafted. The median time to engraftment was 19 days, but the range went as high as 35 days. “The 35 was one of our cord blood recipients,” she noted.
Median time to platelet engraftment was 20 days, and median CD3 and CD33 chimerism at day 80 were 88% and 100%, respectively.
Acute grades II-IV GVHD occurred in 70% of patients, but just 15% of these cases were grades III or IV, she said.
Chronic GVHD occurred in 35% of patients, including two severe cases. Two patients relapsed, including one at 6 months with marrow blast and one at 2 years with myeloid sarcoma. Two treatment-related deaths occurred, including one each at days 54 and 81.
The strategy of overlapping a JAK inhibitor with conditioning chemotherapy was safe, and “better in that we haven’t seen any cytokine release syndrome,” she concluded, adding that no graft failures occurred and grades III-IV acute and severe chronic GVHD were encouragingly infrequent.
Future studies should look at the optimal amount of time for JAK inhibitor therapy prior to transplant and whether it’s safe to continue JAK inhibitors through transplant, she said.
“Some of the work in Germany has shown that JAK inhibitors are safe to include up to day 28 through transplant, and that’s something that we’re looking to explore,” she noted.
Dr. Salit reported having no financial disclosures. This study was sponsored by the Fred Hutchinson Cancer Research Center.
SOURCE: Salit R et al. BMT Tandem Meetings, Abstract 17.
SALT LAKE CITY – The use of Janus kinase (JAK) inhibitor therapy prior to hematopoietic stem cell transplantation is safe and may improve posttransplant survival in patients with myelofibrosis, according to findings from an ongoing prospective phase 2 study.
The 1-year overall survival rate among the 28 initial patients in the single-center study of JAK inhibitor therapy followed by myeloablative or reduced-intensity hematopoietic cell transplantation (HCT) was 93%. The 2-year survival rate was 89%, compared with 54% in a closely matched historical cohort of intermediate-2–risk patients who did not receive pre-HCT JAK inhibitor therapy, Rachel B. Salit, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
“So this is pretty exciting for us,” she added, explaining that allogeneic HCT, which is currently indicated only for patients with intermediate-2– or high-risk disease on the Dynamic International Prognostic Scoring System (DIPSS), remains the only curative treatment option for patients with myelofibrosis.
“Transplant outcomes have been associated with DIPSS and DIPSS+ risk scores,” she said, adding that a study demonstrating that association showed a 54% survival rate at 3 years in patients with intermediate-2–risk disease. “Then JAK-2 inhibitors came down the pipe, and they are also indicated for patients with DIPSS intermediate-2– and high-risk disease. They’ve been shown to decrease spleen size, increase quality of life scores, decrease cytokine levels, and improve constitutional symptoms.”
Posttransplant benefits of pre-HCT JAK inhibitor therapy could include improved graft function because of decreased spleen size and cytokines, potentially decreased severe graft-versus-host disease (GVHD), and decreased nonrelapse mortality.
“Our hypothesis was that the use of JAK inhibitors before transplant in patients with myelofibrosis – by decreasing inflammation, improving constitutional symptoms, and reducing splenomegaly – would result in a decreased DIPSS score” and improved posttransplant survival, Dr. Salit said.
Study participants were patients aged 18 years and older (median of 53 years) with primary or secondary myelofibrosis (14 each). About two-thirds of the study participants were men. Prior to JAK inhibitor therapy, 2 patients were low risk, 10 patients were intermediate-1 risk, and 16 patients were intermediate-2 risk according to the DIPSS.
They were given ruxolitinib (Jakafi) for at least 8 weeks prior to HCT (median of 7 months, but up to 3 years), and the treatment was tapered over 1-2 weeks through day 2 or 3 of conditioning chemotherapy, depending on the conditioning regimen. Conditioning regimens were determined by the physician based on donor type.
“After the ruxolitinib, we had 6 patients who were intermediate-1 and 21 who were intermediate-2, so in that way they failed to meet that hypothesis,” Dr. Salit said. This happened because the patients became anemic, so they gained points on their DIPSS scores for declining constitutional symptoms.
Of the 28 participants, 23 received myeloablative HCT, and 5 received reduced-intensity HCT.
“We had a mixture of related, unrelated, and cord blood recipients,” she noted.
At a median follow-up of just over 1 year, and at up to 3 years in some patients, no cases of cytokine release syndrome have occurred with the overlap of ruxolitinib and conditioning chemotherapy, and there have been no graft failures. All patients, including cord blood recipients, engrafted. The median time to engraftment was 19 days, but the range went as high as 35 days. “The 35 was one of our cord blood recipients,” she noted.
Median time to platelet engraftment was 20 days, and median CD3 and CD33 chimerism at day 80 were 88% and 100%, respectively.
Acute grades II-IV GVHD occurred in 70% of patients, but just 15% of these cases were grades III or IV, she said.
Chronic GVHD occurred in 35% of patients, including two severe cases. Two patients relapsed, including one at 6 months with marrow blast and one at 2 years with myeloid sarcoma. Two treatment-related deaths occurred, including one each at days 54 and 81.
The strategy of overlapping a JAK inhibitor with conditioning chemotherapy was safe, and “better in that we haven’t seen any cytokine release syndrome,” she concluded, adding that no graft failures occurred and grades III-IV acute and severe chronic GVHD were encouragingly infrequent.
Future studies should look at the optimal amount of time for JAK inhibitor therapy prior to transplant and whether it’s safe to continue JAK inhibitors through transplant, she said.
“Some of the work in Germany has shown that JAK inhibitors are safe to include up to day 28 through transplant, and that’s something that we’re looking to explore,” she noted.
Dr. Salit reported having no financial disclosures. This study was sponsored by the Fred Hutchinson Cancer Research Center.
SOURCE: Salit R et al. BMT Tandem Meetings, Abstract 17.
SALT LAKE CITY – The use of Janus kinase (JAK) inhibitor therapy prior to hematopoietic stem cell transplantation is safe and may improve posttransplant survival in patients with myelofibrosis, according to findings from an ongoing prospective phase 2 study.
The 1-year overall survival rate among the 28 initial patients in the single-center study of JAK inhibitor therapy followed by myeloablative or reduced-intensity hematopoietic cell transplantation (HCT) was 93%. The 2-year survival rate was 89%, compared with 54% in a closely matched historical cohort of intermediate-2–risk patients who did not receive pre-HCT JAK inhibitor therapy, Rachel B. Salit, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
“So this is pretty exciting for us,” she added, explaining that allogeneic HCT, which is currently indicated only for patients with intermediate-2– or high-risk disease on the Dynamic International Prognostic Scoring System (DIPSS), remains the only curative treatment option for patients with myelofibrosis.
“Transplant outcomes have been associated with DIPSS and DIPSS+ risk scores,” she said, adding that a study demonstrating that association showed a 54% survival rate at 3 years in patients with intermediate-2–risk disease. “Then JAK-2 inhibitors came down the pipe, and they are also indicated for patients with DIPSS intermediate-2– and high-risk disease. They’ve been shown to decrease spleen size, increase quality of life scores, decrease cytokine levels, and improve constitutional symptoms.”
Posttransplant benefits of pre-HCT JAK inhibitor therapy could include improved graft function because of decreased spleen size and cytokines, potentially decreased severe graft-versus-host disease (GVHD), and decreased nonrelapse mortality.
“Our hypothesis was that the use of JAK inhibitors before transplant in patients with myelofibrosis – by decreasing inflammation, improving constitutional symptoms, and reducing splenomegaly – would result in a decreased DIPSS score” and improved posttransplant survival, Dr. Salit said.
Study participants were patients aged 18 years and older (median of 53 years) with primary or secondary myelofibrosis (14 each). About two-thirds of the study participants were men. Prior to JAK inhibitor therapy, 2 patients were low risk, 10 patients were intermediate-1 risk, and 16 patients were intermediate-2 risk according to the DIPSS.
They were given ruxolitinib (Jakafi) for at least 8 weeks prior to HCT (median of 7 months, but up to 3 years), and the treatment was tapered over 1-2 weeks through day 2 or 3 of conditioning chemotherapy, depending on the conditioning regimen. Conditioning regimens were determined by the physician based on donor type.
“After the ruxolitinib, we had 6 patients who were intermediate-1 and 21 who were intermediate-2, so in that way they failed to meet that hypothesis,” Dr. Salit said. This happened because the patients became anemic, so they gained points on their DIPSS scores for declining constitutional symptoms.
Of the 28 participants, 23 received myeloablative HCT, and 5 received reduced-intensity HCT.
“We had a mixture of related, unrelated, and cord blood recipients,” she noted.
At a median follow-up of just over 1 year, and at up to 3 years in some patients, no cases of cytokine release syndrome have occurred with the overlap of ruxolitinib and conditioning chemotherapy, and there have been no graft failures. All patients, including cord blood recipients, engrafted. The median time to engraftment was 19 days, but the range went as high as 35 days. “The 35 was one of our cord blood recipients,” she noted.
Median time to platelet engraftment was 20 days, and median CD3 and CD33 chimerism at day 80 were 88% and 100%, respectively.
Acute grades II-IV GVHD occurred in 70% of patients, but just 15% of these cases were grades III or IV, she said.
Chronic GVHD occurred in 35% of patients, including two severe cases. Two patients relapsed, including one at 6 months with marrow blast and one at 2 years with myeloid sarcoma. Two treatment-related deaths occurred, including one each at days 54 and 81.
The strategy of overlapping a JAK inhibitor with conditioning chemotherapy was safe, and “better in that we haven’t seen any cytokine release syndrome,” she concluded, adding that no graft failures occurred and grades III-IV acute and severe chronic GVHD were encouragingly infrequent.
Future studies should look at the optimal amount of time for JAK inhibitor therapy prior to transplant and whether it’s safe to continue JAK inhibitors through transplant, she said.
“Some of the work in Germany has shown that JAK inhibitors are safe to include up to day 28 through transplant, and that’s something that we’re looking to explore,” she noted.
Dr. Salit reported having no financial disclosures. This study was sponsored by the Fred Hutchinson Cancer Research Center.
SOURCE: Salit R et al. BMT Tandem Meetings, Abstract 17.
REPORTING FROM THE 2018 BMT TANDEM MEETINGS
Key clinical point:
Major finding: The 2-year overall survival rate was 89%.
Study details: Findings in 28 patients from an ongoing prospective phase 2 study.
Disclosures: Dr. Salit reported having no financial disclosures. The study was sponsored by the Fred Hutchinson Cancer Research Center in Seattle.
Source: Salit R et al. BMT Tandem Meetings, Abstract 17.