Cellular Therapy

SALT LAKE CITY – Scores of 3 or higher on the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) are associated with an increased risk of posttransplant mortality in certain patients undergoing allogeneic HCT for nonmalignant disease, according to findings from a review of more than 4,000 patients.

The exception was in patients undergoing HCT for hemoglobinopathies, Larisa Broglie, 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.

The findings of the study, which is the largest to date to validate the usefulness of the HCT-CI for risk assessment in HCT patients with nonmalignant disease, have important implications for patient counseling and decision making, said Dr. Broglie of the Medical College of Wisconsin, Milwaukee.

Of 4,083 children and adults who underwent a first allogeneic HCT for a nonmalignant disease between 2007 and 2014 and who had sufficient follow-up (median, 39 months), 61% had an HCT-CI score of 0, 20% had a score of 1-2, and 19% had a score of 3 or higher.

[email protected]

SOURCE: Broglie L et al. Abstract 16.

SALT LAKE CITY – Scores of 3 or higher on the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) are associated with an increased risk of posttransplant mortality in certain patients undergoing allogeneic HCT for nonmalignant disease, according to findings from a review of more than 4,000 patients.

The exception was in patients undergoing HCT for hemoglobinopathies, Larisa Broglie, 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.

The findings of the study, which is the largest to date to validate the usefulness of the HCT-CI for risk assessment in HCT patients with nonmalignant disease, have important implications for patient counseling and decision making, said Dr. Broglie of the Medical College of Wisconsin, Milwaukee.

Of 4,083 children and adults who underwent a first allogeneic HCT for a nonmalignant disease between 2007 and 2014 and who had sufficient follow-up (median, 39 months), 61% had an HCT-CI score of 0, 20% had a score of 1-2, and 19% had a score of 3 or higher.

[email protected]

SOURCE: Broglie L et al. Abstract 16.

SALT LAKE CITY – Scores of 3 or higher on the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) are associated with an increased risk of posttransplant mortality in certain patients undergoing allogeneic HCT for nonmalignant disease, according to findings from a review of more than 4,000 patients.

The exception was in patients undergoing HCT for hemoglobinopathies, Larisa Broglie, 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.

The findings of the study, which is the largest to date to validate the usefulness of the HCT-CI for risk assessment in HCT patients with nonmalignant disease, have important implications for patient counseling and decision making, said Dr. Broglie of the Medical College of Wisconsin, Milwaukee.

Of 4,083 children and adults who underwent a first allogeneic HCT for a nonmalignant disease between 2007 and 2014 and who had sufficient follow-up (median, 39 months), 61% had an HCT-CI score of 0, 20% had a score of 1-2, and 19% had a score of 3 or higher.

[email protected]

SOURCE: Broglie L et al. Abstract 16.

Tisagenlecleucel was associated with durable remission and long-term persistence for younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to the results of a multicenter, multicontinent, phase 2 trial published in the New England Journal of Medicine.

Shannon L. Maude, MD, PhD, of the Children’s Hospital of Philadelphia and her coauthors reported that the anti-CD19 chimeric antigen receptor (CAR) therapy was highly toxic, but the effects were usually mitigated. Additionally, the investigators showed feasibility of a global supply chain for distribution of the therapy.

The investigators evaluated data from 75 patients with at least 5% lymphoblasts in their bone marrow at the time of screening. Patients were aged 3 years or older at the time of screening but were no older than 21 years of age at the time of diagnosis.

For 50 patients evaluated at the interim analysis, the primary endpoint of overall remission at 3 months was met, and the overall remission rate was 82% (P less than .001).

An updated analysis showed that 81% of 75 patients who had at least 3 months of follow-up experienced overall remission (95% confidence interval, 71-89). A total of 45 of those patients experienced complete remission, and 16 had complete remission with incomplete hematologic recovery.

Event-free survival was experienced by 73% of patients at 6 months and 50% of patients at 12 months. Overall survival was 90% at 6 months and 76% at 12 months, the investigators reported.

Before tisagenlecleucel infusion, 96% of patients received lymphodepleting chemotherapy. The administration of chemotherapy was not done at the discretion of the investigator if a patient had leukopenia.

The median duration of remission was not reached, and the persistence of tisagenlecleucel in the blood was observed for as long as 20 months.

“The remissions were durable, with a 6-month relapse-free survival rate of 80%,” the investigators wrote. “The durability of the clinical response was associated with persistence of tisagenlecleucel in peripheral blood and with persistent B-cell aplasia.”

The phase 1 study of tisagenlecleucel infusion therapy for younger patients with B-cell ALL showed the toxic nature of the therapy, so investigators were not surprised by the safety data they found. Nearly three-quarters of patients who were evaluated in the study experienced a grade 3 or 4 tisagenlecleucel-related adverse event. Cytokine release syndrome occurred in 77% of patients.

Previously reported data regarding anti-CD19 CAR T-cell therapy for ALL came from single-center studies where manufacturing occurred on site, but the current study employed a global, multicenter supply chain, according to the investigators.

“The toxicity and efficacy of tisagenlecleucel [in this study] were consistent with those in the single-center study, and the feasibility of a global supply chain was demonstrated,” they wrote. “Because this study used cryopreserved leukapheresis product, it did not require fresh product and an open manufacture slot for enrollment.”

This research was sponsored and designed by Novartis Pharmaceuticals. Dr. Maude reported having received personal fees from Novartis as well as grant funding from St. Baldrick’s Foundation.
 

[email protected]

SOURCE: Maude SL, et al. N Engl J Med. 2018;378:439-48.

Tisagenlecleucel was associated with durable remission and long-term persistence for younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to the results of a multicenter, multicontinent, phase 2 trial published in the New England Journal of Medicine.

Shannon L. Maude, MD, PhD, of the Children’s Hospital of Philadelphia and her coauthors reported that the anti-CD19 chimeric antigen receptor (CAR) therapy was highly toxic, but the effects were usually mitigated. Additionally, the investigators showed feasibility of a global supply chain for distribution of the therapy.

The investigators evaluated data from 75 patients with at least 5% lymphoblasts in their bone marrow at the time of screening. Patients were aged 3 years or older at the time of screening but were no older than 21 years of age at the time of diagnosis.

For 50 patients evaluated at the interim analysis, the primary endpoint of overall remission at 3 months was met, and the overall remission rate was 82% (P less than .001).

An updated analysis showed that 81% of 75 patients who had at least 3 months of follow-up experienced overall remission (95% confidence interval, 71-89). A total of 45 of those patients experienced complete remission, and 16 had complete remission with incomplete hematologic recovery.

Event-free survival was experienced by 73% of patients at 6 months and 50% of patients at 12 months. Overall survival was 90% at 6 months and 76% at 12 months, the investigators reported.

Before tisagenlecleucel infusion, 96% of patients received lymphodepleting chemotherapy. The administration of chemotherapy was not done at the discretion of the investigator if a patient had leukopenia.

The median duration of remission was not reached, and the persistence of tisagenlecleucel in the blood was observed for as long as 20 months.

“The remissions were durable, with a 6-month relapse-free survival rate of 80%,” the investigators wrote. “The durability of the clinical response was associated with persistence of tisagenlecleucel in peripheral blood and with persistent B-cell aplasia.”

The phase 1 study of tisagenlecleucel infusion therapy for younger patients with B-cell ALL showed the toxic nature of the therapy, so investigators were not surprised by the safety data they found. Nearly three-quarters of patients who were evaluated in the study experienced a grade 3 or 4 tisagenlecleucel-related adverse event. Cytokine release syndrome occurred in 77% of patients.

Previously reported data regarding anti-CD19 CAR T-cell therapy for ALL came from single-center studies where manufacturing occurred on site, but the current study employed a global, multicenter supply chain, according to the investigators.

“The toxicity and efficacy of tisagenlecleucel [in this study] were consistent with those in the single-center study, and the feasibility of a global supply chain was demonstrated,” they wrote. “Because this study used cryopreserved leukapheresis product, it did not require fresh product and an open manufacture slot for enrollment.”

This research was sponsored and designed by Novartis Pharmaceuticals. Dr. Maude reported having received personal fees from Novartis as well as grant funding from St. Baldrick’s Foundation.
 

[email protected]

SOURCE: Maude SL, et al. N Engl J Med. 2018;378:439-48.

Tisagenlecleucel was associated with durable remission and long-term persistence for younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to the results of a multicenter, multicontinent, phase 2 trial published in the New England Journal of Medicine.

Shannon L. Maude, MD, PhD, of the Children’s Hospital of Philadelphia and her coauthors reported that the anti-CD19 chimeric antigen receptor (CAR) therapy was highly toxic, but the effects were usually mitigated. Additionally, the investigators showed feasibility of a global supply chain for distribution of the therapy.

The investigators evaluated data from 75 patients with at least 5% lymphoblasts in their bone marrow at the time of screening. Patients were aged 3 years or older at the time of screening but were no older than 21 years of age at the time of diagnosis.

For 50 patients evaluated at the interim analysis, the primary endpoint of overall remission at 3 months was met, and the overall remission rate was 82% (P less than .001).

An updated analysis showed that 81% of 75 patients who had at least 3 months of follow-up experienced overall remission (95% confidence interval, 71-89). A total of 45 of those patients experienced complete remission, and 16 had complete remission with incomplete hematologic recovery.

Event-free survival was experienced by 73% of patients at 6 months and 50% of patients at 12 months. Overall survival was 90% at 6 months and 76% at 12 months, the investigators reported.

Before tisagenlecleucel infusion, 96% of patients received lymphodepleting chemotherapy. The administration of chemotherapy was not done at the discretion of the investigator if a patient had leukopenia.

The median duration of remission was not reached, and the persistence of tisagenlecleucel in the blood was observed for as long as 20 months.

“The remissions were durable, with a 6-month relapse-free survival rate of 80%,” the investigators wrote. “The durability of the clinical response was associated with persistence of tisagenlecleucel in peripheral blood and with persistent B-cell aplasia.”

The phase 1 study of tisagenlecleucel infusion therapy for younger patients with B-cell ALL showed the toxic nature of the therapy, so investigators were not surprised by the safety data they found. Nearly three-quarters of patients who were evaluated in the study experienced a grade 3 or 4 tisagenlecleucel-related adverse event. Cytokine release syndrome occurred in 77% of patients.

Previously reported data regarding anti-CD19 CAR T-cell therapy for ALL came from single-center studies where manufacturing occurred on site, but the current study employed a global, multicenter supply chain, according to the investigators.

“The toxicity and efficacy of tisagenlecleucel [in this study] were consistent with those in the single-center study, and the feasibility of a global supply chain was demonstrated,” they wrote. “Because this study used cryopreserved leukapheresis product, it did not require fresh product and an open manufacture slot for enrollment.”

This research was sponsored and designed by Novartis Pharmaceuticals. Dr. Maude reported having received personal fees from Novartis as well as grant funding from St. Baldrick’s Foundation.
 

[email protected]

SOURCE: Maude SL, et al. N Engl J Med. 2018;378:439-48.

People with rheumatologic diseases and cancer appear to be at no higher risk of having an adverse event or disease flare if they receive checkpoint inhibitor therapy, compared with the general population, experience from the Mayo Clinic suggests.

In a brief report published in Arthritis and Rheumatology, a team from the Mayo Clinic in Rochester, Minn., reported on 16 patients with rheumatologic diseases who received cancer immunotherapy. They found that only a minority experienced a flare of their disease or another immune-related event.

The rate of severe immune-related adverse effects (IRAEs) with a single immune checkpoint inhibitor (ICI) has been reported to be less than 2% among the average population. However, less is known about patients with underlying rheumatologic disease, largely because initial trials of ICIs had excluded patients with autoimmune diseases for fear the treatment would induce a disease flare, the researchers noted.

Small studies have suggested that people with inflammatory arthritis or connective tissue diseases have higher rates of IRAEs with immunotherapy, but it is unclear how often these events represented flares of their disease or new autoimmune events, and whether the events had any predictive significance for cancer survival.

In this study, researchers performed a retrospective review of medical records and identified 16 patients with rheumatologic diseases who had received checkpoint inhibitor therapy at the Mayo Clinic between 2011 and 2016.

The most common rheumatologic diseases among the 16 patients were rheumatoid arthritis, polymyalgia rheumatica, Sjögren’s syndrome, and systemic lupus erythematosus, and the most common cancers were malignant melanoma, pulmonary malignancies, and non-Hodgkin lymphoma. Seven of the patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatologic disease upon initiation of a checkpoint inhibitor.

Ten patients had received a prior disease-modifying antirheumatic drug, but only two patients were still taking this at the time of ICI initiation.

Results showed that six of the patients (38%) had an IRAE or flare of their rheumatologic disease, two were graded as mild. All of the patients responded well to glucocorticoids and discontinuation of therapy. The most common event was colitis and just one patient had a flare of rheumatologic disease.

“This is consistent with what is currently known about the management of IRAEs,” the research team wrote. “This study adds further support to the emerging notion that the rate of IRAEs is not necessarily higher in this group compared to the general population.”

The type and severity of rheumatologic disease may play an important role in both the risk of disease flare and IRAEs, a factor that they were unable to assess in the current study, the researchers wrote.

“Further large, prospective studies are needed to address the link between the type, severity, and concurrent rheumatologic disease activity on the risk of flare and IRAE. It is possible that patients with more severe or active disease are at higher risk for these complications,” they wrote.

While patients in the study did not appear to have significantly increased incidence or severity of adverse effects, the research team advised that “treatment decisions must factor in clinical judgement.”

They noted that some studies had proposed predictive biomarkers, pretreatment workup, and monitoring, but this advice was based on a small body of evidence.

“Larger, prospective studies will be necessary to validate these findings and establish evidence-based guidelines for appropriate identification and rating of the rheumatologic IRAEs as well as their treatment, such that patients can continue to receive potentially life-saving cancer treatments,” they wrote.

One of the researchers reported advisory board membership with Bristol-Myers Squibb.

[email protected]

SOURCE: Richter M et al. Arthritis Rheumatol. 2018 Jan 24. doi: 10.1002/art.40397.

People with rheumatologic diseases and cancer appear to be at no higher risk of having an adverse event or disease flare if they receive checkpoint inhibitor therapy, compared with the general population, experience from the Mayo Clinic suggests.

In a brief report published in Arthritis and Rheumatology, a team from the Mayo Clinic in Rochester, Minn., reported on 16 patients with rheumatologic diseases who received cancer immunotherapy. They found that only a minority experienced a flare of their disease or another immune-related event.

The rate of severe immune-related adverse effects (IRAEs) with a single immune checkpoint inhibitor (ICI) has been reported to be less than 2% among the average population. However, less is known about patients with underlying rheumatologic disease, largely because initial trials of ICIs had excluded patients with autoimmune diseases for fear the treatment would induce a disease flare, the researchers noted.

Small studies have suggested that people with inflammatory arthritis or connective tissue diseases have higher rates of IRAEs with immunotherapy, but it is unclear how often these events represented flares of their disease or new autoimmune events, and whether the events had any predictive significance for cancer survival.

In this study, researchers performed a retrospective review of medical records and identified 16 patients with rheumatologic diseases who had received checkpoint inhibitor therapy at the Mayo Clinic between 2011 and 2016.

The most common rheumatologic diseases among the 16 patients were rheumatoid arthritis, polymyalgia rheumatica, Sjögren’s syndrome, and systemic lupus erythematosus, and the most common cancers were malignant melanoma, pulmonary malignancies, and non-Hodgkin lymphoma. Seven of the patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatologic disease upon initiation of a checkpoint inhibitor.

Ten patients had received a prior disease-modifying antirheumatic drug, but only two patients were still taking this at the time of ICI initiation.

Results showed that six of the patients (38%) had an IRAE or flare of their rheumatologic disease, two were graded as mild. All of the patients responded well to glucocorticoids and discontinuation of therapy. The most common event was colitis and just one patient had a flare of rheumatologic disease.

“This is consistent with what is currently known about the management of IRAEs,” the research team wrote. “This study adds further support to the emerging notion that the rate of IRAEs is not necessarily higher in this group compared to the general population.”

The type and severity of rheumatologic disease may play an important role in both the risk of disease flare and IRAEs, a factor that they were unable to assess in the current study, the researchers wrote.

“Further large, prospective studies are needed to address the link between the type, severity, and concurrent rheumatologic disease activity on the risk of flare and IRAE. It is possible that patients with more severe or active disease are at higher risk for these complications,” they wrote.

While patients in the study did not appear to have significantly increased incidence or severity of adverse effects, the research team advised that “treatment decisions must factor in clinical judgement.”

They noted that some studies had proposed predictive biomarkers, pretreatment workup, and monitoring, but this advice was based on a small body of evidence.

“Larger, prospective studies will be necessary to validate these findings and establish evidence-based guidelines for appropriate identification and rating of the rheumatologic IRAEs as well as their treatment, such that patients can continue to receive potentially life-saving cancer treatments,” they wrote.

One of the researchers reported advisory board membership with Bristol-Myers Squibb.

[email protected]

SOURCE: Richter M et al. Arthritis Rheumatol. 2018 Jan 24. doi: 10.1002/art.40397.

People with rheumatologic diseases and cancer appear to be at no higher risk of having an adverse event or disease flare if they receive checkpoint inhibitor therapy, compared with the general population, experience from the Mayo Clinic suggests.

In a brief report published in Arthritis and Rheumatology, a team from the Mayo Clinic in Rochester, Minn., reported on 16 patients with rheumatologic diseases who received cancer immunotherapy. They found that only a minority experienced a flare of their disease or another immune-related event.

The rate of severe immune-related adverse effects (IRAEs) with a single immune checkpoint inhibitor (ICI) has been reported to be less than 2% among the average population. However, less is known about patients with underlying rheumatologic disease, largely because initial trials of ICIs had excluded patients with autoimmune diseases for fear the treatment would induce a disease flare, the researchers noted.

Small studies have suggested that people with inflammatory arthritis or connective tissue diseases have higher rates of IRAEs with immunotherapy, but it is unclear how often these events represented flares of their disease or new autoimmune events, and whether the events had any predictive significance for cancer survival.

In this study, researchers performed a retrospective review of medical records and identified 16 patients with rheumatologic diseases who had received checkpoint inhibitor therapy at the Mayo Clinic between 2011 and 2016.

The most common rheumatologic diseases among the 16 patients were rheumatoid arthritis, polymyalgia rheumatica, Sjögren’s syndrome, and systemic lupus erythematosus, and the most common cancers were malignant melanoma, pulmonary malignancies, and non-Hodgkin lymphoma. Seven of the patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatologic disease upon initiation of a checkpoint inhibitor.

Ten patients had received a prior disease-modifying antirheumatic drug, but only two patients were still taking this at the time of ICI initiation.

Results showed that six of the patients (38%) had an IRAE or flare of their rheumatologic disease, two were graded as mild. All of the patients responded well to glucocorticoids and discontinuation of therapy. The most common event was colitis and just one patient had a flare of rheumatologic disease.

“This is consistent with what is currently known about the management of IRAEs,” the research team wrote. “This study adds further support to the emerging notion that the rate of IRAEs is not necessarily higher in this group compared to the general population.”

The type and severity of rheumatologic disease may play an important role in both the risk of disease flare and IRAEs, a factor that they were unable to assess in the current study, the researchers wrote.

“Further large, prospective studies are needed to address the link between the type, severity, and concurrent rheumatologic disease activity on the risk of flare and IRAE. It is possible that patients with more severe or active disease are at higher risk for these complications,” they wrote.

While patients in the study did not appear to have significantly increased incidence or severity of adverse effects, the research team advised that “treatment decisions must factor in clinical judgement.”

They noted that some studies had proposed predictive biomarkers, pretreatment workup, and monitoring, but this advice was based on a small body of evidence.

“Larger, prospective studies will be necessary to validate these findings and establish evidence-based guidelines for appropriate identification and rating of the rheumatologic IRAEs as well as their treatment, such that patients can continue to receive potentially life-saving cancer treatments,” they wrote.

One of the researchers reported advisory board membership with Bristol-Myers Squibb.

[email protected]

SOURCE: Richter M et al. Arthritis Rheumatol. 2018 Jan 24. doi: 10.1002/art.40397.

Undergoing a second allogeneic bone or marrow transplant (BMT) is a feasible strategy for patients who have relapsed after their first transplantation, according to findings reported in Biology of Blood and Marrow Transplantation.

Specifically, there may be an advantage to selecting a donor with a new mismatched haplotype after a failed HLA-matched allograft. Among patients who had a second graft transplanted that did not harbor a new mismatched haplotype, median survival was 552 days (95% CI, 376-2,950+). But median survival was not reached in the cohort whose allograft contained a new mismatched haplotype (hazard ratio, 0.36; 95% confidence interval, 0.14-0.9; P = .02).

“In the case of a failed HLA-matched transplantation, when haplotype loss would not be favored through selective pressure and thus would not provide a mechanism of relapse, switching to a different haploidentical donor may be beneficial by increasing major histocompatibility mismatch,” Philip H. Imus, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and colleagues wrote.

For this retrospective review, the researchers examined 40 consecutive patients who underwent a second BMT for a relapsed hematologic malignancy at a single institution between 2005 and 2014. In all, 21 patients had their first allograft from a haploidentical donor, with 14 of these patients receiving a second haploidentical transplant (8 from a donor sharing the same shared haplotype as the first donor and 6 from a second donor sharing the other haplotype).

The other 19 patients received their first allograft from a fully matched donor, with 14 patients receiving a haploidentical allograft at the second transplantation and 5 receiving a second matched allograft. Overall, a total of 20 patients had a second allograft with a new mismatched haplotype.

The median overall survival for the six patients who were retransplantated with an HLA-haploidentical donor sharing the different haplotype from the first haploidentical donor had not been reached, compared with 502 days (95% CI, 317-2,950+) for the eight patients with a second haplo allograft that shared the same haplotype (HR, 0.37; 95% CI, 0.08 to 1.7; P = .16).

The median event free survival was also superior among those retransplanted with a new mismatched haplotype (not reached vs. 401 days; HR, .50; 95% CI, .22-1.14, P = .09).

A higher risk of mortality was observed in patients who had relapsed within 6 months of their first transplantation (HR, 2.49; 95% CI, 1.0-6.2; P = .07), as well as in those who had progressive or refractory disease prior to their second alloBMT (HR, 2.56; 95% CI, 1.03-6.25; P = .06).

“For patients who relapse more than 6 months after a BMT and who achieve remission with salvage therapy, results are very encouraging,” the researchers wrote. “Although a randomized trial to study selecting donors with a new mismatched haplotype may be impractical, larger numbers should provide additional information on the effectiveness of such an approach.”

The researchers reported having no financial disclosures.

SOURCE: Imus P et al. Biol Blood Marrow Transplant. 2017;23:1887-94.

Undergoing a second allogeneic bone or marrow transplant (BMT) is a feasible strategy for patients who have relapsed after their first transplantation, according to findings reported in Biology of Blood and Marrow Transplantation.

Specifically, there may be an advantage to selecting a donor with a new mismatched haplotype after a failed HLA-matched allograft. Among patients who had a second graft transplanted that did not harbor a new mismatched haplotype, median survival was 552 days (95% CI, 376-2,950+). But median survival was not reached in the cohort whose allograft contained a new mismatched haplotype (hazard ratio, 0.36; 95% confidence interval, 0.14-0.9; P = .02).

“In the case of a failed HLA-matched transplantation, when haplotype loss would not be favored through selective pressure and thus would not provide a mechanism of relapse, switching to a different haploidentical donor may be beneficial by increasing major histocompatibility mismatch,” Philip H. Imus, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and colleagues wrote.

For this retrospective review, the researchers examined 40 consecutive patients who underwent a second BMT for a relapsed hematologic malignancy at a single institution between 2005 and 2014. In all, 21 patients had their first allograft from a haploidentical donor, with 14 of these patients receiving a second haploidentical transplant (8 from a donor sharing the same shared haplotype as the first donor and 6 from a second donor sharing the other haplotype).

The other 19 patients received their first allograft from a fully matched donor, with 14 patients receiving a haploidentical allograft at the second transplantation and 5 receiving a second matched allograft. Overall, a total of 20 patients had a second allograft with a new mismatched haplotype.

The median overall survival for the six patients who were retransplantated with an HLA-haploidentical donor sharing the different haplotype from the first haploidentical donor had not been reached, compared with 502 days (95% CI, 317-2,950+) for the eight patients with a second haplo allograft that shared the same haplotype (HR, 0.37; 95% CI, 0.08 to 1.7; P = .16).

The median event free survival was also superior among those retransplanted with a new mismatched haplotype (not reached vs. 401 days; HR, .50; 95% CI, .22-1.14, P = .09).

A higher risk of mortality was observed in patients who had relapsed within 6 months of their first transplantation (HR, 2.49; 95% CI, 1.0-6.2; P = .07), as well as in those who had progressive or refractory disease prior to their second alloBMT (HR, 2.56; 95% CI, 1.03-6.25; P = .06).

“For patients who relapse more than 6 months after a BMT and who achieve remission with salvage therapy, results are very encouraging,” the researchers wrote. “Although a randomized trial to study selecting donors with a new mismatched haplotype may be impractical, larger numbers should provide additional information on the effectiveness of such an approach.”

The researchers reported having no financial disclosures.

SOURCE: Imus P et al. Biol Blood Marrow Transplant. 2017;23:1887-94.

Undergoing a second allogeneic bone or marrow transplant (BMT) is a feasible strategy for patients who have relapsed after their first transplantation, according to findings reported in Biology of Blood and Marrow Transplantation.

Specifically, there may be an advantage to selecting a donor with a new mismatched haplotype after a failed HLA-matched allograft. Among patients who had a second graft transplanted that did not harbor a new mismatched haplotype, median survival was 552 days (95% CI, 376-2,950+). But median survival was not reached in the cohort whose allograft contained a new mismatched haplotype (hazard ratio, 0.36; 95% confidence interval, 0.14-0.9; P = .02).

“In the case of a failed HLA-matched transplantation, when haplotype loss would not be favored through selective pressure and thus would not provide a mechanism of relapse, switching to a different haploidentical donor may be beneficial by increasing major histocompatibility mismatch,” Philip H. Imus, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and colleagues wrote.

For this retrospective review, the researchers examined 40 consecutive patients who underwent a second BMT for a relapsed hematologic malignancy at a single institution between 2005 and 2014. In all, 21 patients had their first allograft from a haploidentical donor, with 14 of these patients receiving a second haploidentical transplant (8 from a donor sharing the same shared haplotype as the first donor and 6 from a second donor sharing the other haplotype).

The other 19 patients received their first allograft from a fully matched donor, with 14 patients receiving a haploidentical allograft at the second transplantation and 5 receiving a second matched allograft. Overall, a total of 20 patients had a second allograft with a new mismatched haplotype.

The median overall survival for the six patients who were retransplantated with an HLA-haploidentical donor sharing the different haplotype from the first haploidentical donor had not been reached, compared with 502 days (95% CI, 317-2,950+) for the eight patients with a second haplo allograft that shared the same haplotype (HR, 0.37; 95% CI, 0.08 to 1.7; P = .16).

The median event free survival was also superior among those retransplanted with a new mismatched haplotype (not reached vs. 401 days; HR, .50; 95% CI, .22-1.14, P = .09).

A higher risk of mortality was observed in patients who had relapsed within 6 months of their first transplantation (HR, 2.49; 95% CI, 1.0-6.2; P = .07), as well as in those who had progressive or refractory disease prior to their second alloBMT (HR, 2.56; 95% CI, 1.03-6.25; P = .06).

“For patients who relapse more than 6 months after a BMT and who achieve remission with salvage therapy, results are very encouraging,” the researchers wrote. “Although a randomized trial to study selecting donors with a new mismatched haplotype may be impractical, larger numbers should provide additional information on the effectiveness of such an approach.”

The researchers reported having no financial disclosures.

SOURCE: Imus P et al. Biol Blood Marrow Transplant. 2017;23:1887-94.

Myeloablative autologous hematopoietic stem-cell transplantation shows long-term benefits for patients with severe scleroderma, with improved event-free and overall survival over intravenous cyclophosphamide, according to Keith M. Sullivan, MD, and his associates.

A total of 75 patients with severe scleroderma (diffuse cutaneous systemic sclerosis) underwent randomization to open-label treatment with either transplantation or intravenous cyclophosphamide at an initial dose of 500 mg/m² of body-surface area, followed by 11 monthly infusions of 750 mg/m² with mesna prophylaxis.

Fnaq / Wikimedia Commons / CC BY-SA 4.0

[email protected]

SOURCE: Sullivan K et al. N Engl J Med. 2018;378;35-47.

Myeloablative autologous hematopoietic stem-cell transplantation shows long-term benefits for patients with severe scleroderma, with improved event-free and overall survival over intravenous cyclophosphamide, according to Keith M. Sullivan, MD, and his associates.

A total of 75 patients with severe scleroderma (diffuse cutaneous systemic sclerosis) underwent randomization to open-label treatment with either transplantation or intravenous cyclophosphamide at an initial dose of 500 mg/m² of body-surface area, followed by 11 monthly infusions of 750 mg/m² with mesna prophylaxis.

Fnaq / Wikimedia Commons / CC BY-SA 4.0

[email protected]

SOURCE: Sullivan K et al. N Engl J Med. 2018;378;35-47.

Myeloablative autologous hematopoietic stem-cell transplantation shows long-term benefits for patients with severe scleroderma, with improved event-free and overall survival over intravenous cyclophosphamide, according to Keith M. Sullivan, MD, and his associates.

A total of 75 patients with severe scleroderma (diffuse cutaneous systemic sclerosis) underwent randomization to open-label treatment with either transplantation or intravenous cyclophosphamide at an initial dose of 500 mg/m² of body-surface area, followed by 11 monthly infusions of 750 mg/m² with mesna prophylaxis.

Fnaq / Wikimedia Commons / CC BY-SA 4.0

[email protected]

SOURCE: Sullivan K et al. N Engl J Med. 2018;378;35-47.

ATLANTA – Closely monitoring for cytokine release syndrome (CRS) and starting anticytokine therapy early can prevent life-threatening organ toxicities in recipients of chimeric antigen receptor (CAR) T-cell therapy, according to Daniel W. Lee III, MD.

There’s no evidence that early anticytokine therapy impairs antitumor response, he noted. “If you wait to give anticytokine therapy until a patient is intubated, it’s too late,” Dr. Lee said at the annual meeting of the American Society of Hematology. “If you wait until a patient has been hypotensive for days, it’s probably too late. If you intervene earlier, you can avoid intubation.”

ATLANTA – Closely monitoring for cytokine release syndrome (CRS) and starting anticytokine therapy early can prevent life-threatening organ toxicities in recipients of chimeric antigen receptor (CAR) T-cell therapy, according to Daniel W. Lee III, MD.

There’s no evidence that early anticytokine therapy impairs antitumor response, he noted. “If you wait to give anticytokine therapy until a patient is intubated, it’s too late,” Dr. Lee said at the annual meeting of the American Society of Hematology. “If you wait until a patient has been hypotensive for days, it’s probably too late. If you intervene earlier, you can avoid intubation.”

ATLANTA – Closely monitoring for cytokine release syndrome (CRS) and starting anticytokine therapy early can prevent life-threatening organ toxicities in recipients of chimeric antigen receptor (CAR) T-cell therapy, according to Daniel W. Lee III, MD.

There’s no evidence that early anticytokine therapy impairs antitumor response, he noted. “If you wait to give anticytokine therapy until a patient is intubated, it’s too late,” Dr. Lee said at the annual meeting of the American Society of Hematology. “If you wait until a patient has been hypotensive for days, it’s probably too late. If you intervene earlier, you can avoid intubation.”

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

ATLANTA – A new approach to gene therapy produced rapid T cell reconstruction and normal markers of B-cell and natural killer (NK)-cell function in newly diagnosed infants with X-linked Severe Combined Immunodeficiency (XSCID), according to initial results from a phase 1/2 trial.

Researchers used a regimen of safety-modified lentiviral vector plus reduced-exposure busulfan conditioning in seven newly diagnosed infants and found that it was well tolerated in all patients and quickly improved T-cell immunity in five of seven patients.

Mary Ellen Schneider/Frontline Medical News

ATLANTA – A new approach to gene therapy produced rapid T cell reconstruction and normal markers of B-cell and natural killer (NK)-cell function in newly diagnosed infants with X-linked Severe Combined Immunodeficiency (XSCID), according to initial results from a phase 1/2 trial.

Researchers used a regimen of safety-modified lentiviral vector plus reduced-exposure busulfan conditioning in seven newly diagnosed infants and found that it was well tolerated in all patients and quickly improved T-cell immunity in five of seven patients.

Mary Ellen Schneider/Frontline Medical News

ATLANTA – A new approach to gene therapy produced rapid T cell reconstruction and normal markers of B-cell and natural killer (NK)-cell function in newly diagnosed infants with X-linked Severe Combined Immunodeficiency (XSCID), according to initial results from a phase 1/2 trial.

Researchers used a regimen of safety-modified lentiviral vector plus reduced-exposure busulfan conditioning in seven newly diagnosed infants and found that it was well tolerated in all patients and quickly improved T-cell immunity in five of seven patients.

Mary Ellen Schneider/Frontline Medical News

Post-transplantation cyclophosphamide may help decrease the rate of nonrelapse mortality and graft-versus-host disease (GVHD) in patients who have undergone allogeneic blood or marrow transplantation, according to new findings published in Biology of Blood and Marrow Transplantation.

Even though it is a potentially curative option for patients with poor-risk hematologic malignancies, allogeneic blood or marrow transplantation (alloBMT) has not been commonly used in multiple myeloma because of its association with high nonrelapse mortality and high relapse rates. However, the use of post-transplantation cyclophosphamide (PTCy) in this study led to low rates of both acute and chronic GVHD, which translated to low rates of nonrelapse mortality and maintenance of long-term remissions in a subset of patients with multiple myeloma treated at Johns Hopkins Hospital, Baltimore.

“The favorable toxicity profile of alloBMT using PTCy in patients with MM offers the potential to further explore the use of post-transplantation strategies to improve disease control,” wrote Nilanjan Ghosh, MD, of the Levine Cancer Institute, Charlotte, N.C., and his colleagues.

The researchers examined outcomes of 39 patients with multiple myeloma who underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning.

Patients who underwent myeloablative conditioning received PTCy 50 mg/kg per day (given intravenously on days 3 and 4 after alloBMT) as GVHD prophylaxis, while those who received nonmyeloablative conditioning received PTCy (same dose and schedule) and additional immunosuppression with mycophenolate mofetil 15 mg/kg (orally two to three times daily, up to 1,000 mg/dose on days 4-35 after transplantation).

At a median follow-up of 10.3 years following alloBMT, 23% of the cohort remained alive and without any evidence of disease. The median overall survival was 4.4 years. The 5-year survival probability was 49% (95% confidence interval, 32%-67%) and 10-year survival probability was 43% (95% CI, 29%-62%).

Following transplantation, 10 (26%) patients achieved a complete response, 8 (21%) had a very good partial response, 6 (15%) had a partial response, and 15 (38%) had progressive disease, the investigators reported (Biol Blood Marrow Transplant. 2017 Nov;23[11]:1903-9).

Among the 36 patients with evidence of donor engraftment, the cumulative incidences of grade 2-4 and grade 3 and 4 acute GVHD were 0.41 (95% CI, 0.25-0.57) and 0.08 (95% CI, 0.01-0.16), respectively. For chronic GVHD, the cumulative incidence was 0.13 (95% CI, 0.02-0.23), and the median time to development was 109 days after alloBMT.

The median progression-free survival was 12 months (95% CI, 7.6-40), and the estimated cumulative incidence of relapse was 0.46 (95% CI, 0.3-0.62) at 1 year and 0.56 (95% CI, 0.41-0.72) at 2 years.

In univariate analysis, achievement of a complete response following alloBMT correlated with overall survival. Factors such as the intensity of the alloBMT conditioning regimen, stem cell source, age, and disease response before alloBMT did not appear to impact overall survival.

“Given the low incidence of GVHD and [nonrelapse mortality] in our study, it is possible that post-transplantation maintenance therapies can be used to improve diseases control,” Dr. Ghosh and his associates wrote. “Emerging data suggest that many anticancer agents may be more active after alloBMT than before transplantation.”

The study was funded in part by grants from the National Institutes of Health. The researchers reported having no relevant financial disclosures.

Post-transplantation cyclophosphamide may help decrease the rate of nonrelapse mortality and graft-versus-host disease (GVHD) in patients who have undergone allogeneic blood or marrow transplantation, according to new findings published in Biology of Blood and Marrow Transplantation.

Even though it is a potentially curative option for patients with poor-risk hematologic malignancies, allogeneic blood or marrow transplantation (alloBMT) has not been commonly used in multiple myeloma because of its association with high nonrelapse mortality and high relapse rates. However, the use of post-transplantation cyclophosphamide (PTCy) in this study led to low rates of both acute and chronic GVHD, which translated to low rates of nonrelapse mortality and maintenance of long-term remissions in a subset of patients with multiple myeloma treated at Johns Hopkins Hospital, Baltimore.

“The favorable toxicity profile of alloBMT using PTCy in patients with MM offers the potential to further explore the use of post-transplantation strategies to improve disease control,” wrote Nilanjan Ghosh, MD, of the Levine Cancer Institute, Charlotte, N.C., and his colleagues.

The researchers examined outcomes of 39 patients with multiple myeloma who underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning.

Patients who underwent myeloablative conditioning received PTCy 50 mg/kg per day (given intravenously on days 3 and 4 after alloBMT) as GVHD prophylaxis, while those who received nonmyeloablative conditioning received PTCy (same dose and schedule) and additional immunosuppression with mycophenolate mofetil 15 mg/kg (orally two to three times daily, up to 1,000 mg/dose on days 4-35 after transplantation).

At a median follow-up of 10.3 years following alloBMT, 23% of the cohort remained alive and without any evidence of disease. The median overall survival was 4.4 years. The 5-year survival probability was 49% (95% confidence interval, 32%-67%) and 10-year survival probability was 43% (95% CI, 29%-62%).

Following transplantation, 10 (26%) patients achieved a complete response, 8 (21%) had a very good partial response, 6 (15%) had a partial response, and 15 (38%) had progressive disease, the investigators reported (Biol Blood Marrow Transplant. 2017 Nov;23[11]:1903-9).

Among the 36 patients with evidence of donor engraftment, the cumulative incidences of grade 2-4 and grade 3 and 4 acute GVHD were 0.41 (95% CI, 0.25-0.57) and 0.08 (95% CI, 0.01-0.16), respectively. For chronic GVHD, the cumulative incidence was 0.13 (95% CI, 0.02-0.23), and the median time to development was 109 days after alloBMT.

The median progression-free survival was 12 months (95% CI, 7.6-40), and the estimated cumulative incidence of relapse was 0.46 (95% CI, 0.3-0.62) at 1 year and 0.56 (95% CI, 0.41-0.72) at 2 years.

In univariate analysis, achievement of a complete response following alloBMT correlated with overall survival. Factors such as the intensity of the alloBMT conditioning regimen, stem cell source, age, and disease response before alloBMT did not appear to impact overall survival.

“Given the low incidence of GVHD and [nonrelapse mortality] in our study, it is possible that post-transplantation maintenance therapies can be used to improve diseases control,” Dr. Ghosh and his associates wrote. “Emerging data suggest that many anticancer agents may be more active after alloBMT than before transplantation.”

The study was funded in part by grants from the National Institutes of Health. The researchers reported having no relevant financial disclosures.

Post-transplantation cyclophosphamide may help decrease the rate of nonrelapse mortality and graft-versus-host disease (GVHD) in patients who have undergone allogeneic blood or marrow transplantation, according to new findings published in Biology of Blood and Marrow Transplantation.

Even though it is a potentially curative option for patients with poor-risk hematologic malignancies, allogeneic blood or marrow transplantation (alloBMT) has not been commonly used in multiple myeloma because of its association with high nonrelapse mortality and high relapse rates. However, the use of post-transplantation cyclophosphamide (PTCy) in this study led to low rates of both acute and chronic GVHD, which translated to low rates of nonrelapse mortality and maintenance of long-term remissions in a subset of patients with multiple myeloma treated at Johns Hopkins Hospital, Baltimore.

“The favorable toxicity profile of alloBMT using PTCy in patients with MM offers the potential to further explore the use of post-transplantation strategies to improve disease control,” wrote Nilanjan Ghosh, MD, of the Levine Cancer Institute, Charlotte, N.C., and his colleagues.

The researchers examined outcomes of 39 patients with multiple myeloma who underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning.

Patients who underwent myeloablative conditioning received PTCy 50 mg/kg per day (given intravenously on days 3 and 4 after alloBMT) as GVHD prophylaxis, while those who received nonmyeloablative conditioning received PTCy (same dose and schedule) and additional immunosuppression with mycophenolate mofetil 15 mg/kg (orally two to three times daily, up to 1,000 mg/dose on days 4-35 after transplantation).

At a median follow-up of 10.3 years following alloBMT, 23% of the cohort remained alive and without any evidence of disease. The median overall survival was 4.4 years. The 5-year survival probability was 49% (95% confidence interval, 32%-67%) and 10-year survival probability was 43% (95% CI, 29%-62%).

Following transplantation, 10 (26%) patients achieved a complete response, 8 (21%) had a very good partial response, 6 (15%) had a partial response, and 15 (38%) had progressive disease, the investigators reported (Biol Blood Marrow Transplant. 2017 Nov;23[11]:1903-9).

Among the 36 patients with evidence of donor engraftment, the cumulative incidences of grade 2-4 and grade 3 and 4 acute GVHD were 0.41 (95% CI, 0.25-0.57) and 0.08 (95% CI, 0.01-0.16), respectively. For chronic GVHD, the cumulative incidence was 0.13 (95% CI, 0.02-0.23), and the median time to development was 109 days after alloBMT.

The median progression-free survival was 12 months (95% CI, 7.6-40), and the estimated cumulative incidence of relapse was 0.46 (95% CI, 0.3-0.62) at 1 year and 0.56 (95% CI, 0.41-0.72) at 2 years.

In univariate analysis, achievement of a complete response following alloBMT correlated with overall survival. Factors such as the intensity of the alloBMT conditioning regimen, stem cell source, age, and disease response before alloBMT did not appear to impact overall survival.

“Given the low incidence of GVHD and [nonrelapse mortality] in our study, it is possible that post-transplantation maintenance therapies can be used to improve diseases control,” Dr. Ghosh and his associates wrote. “Emerging data suggest that many anticancer agents may be more active after alloBMT than before transplantation.”

The study was funded in part by grants from the National Institutes of Health. The researchers reported having no relevant financial disclosures.

The Food and Drug Administration has announced a new policy that addresses the rapid growth and development of regenerative medicine products, which include novel cellular therapies, with the aim of ensuring their safety and effectiveness.

“The framework – outlined in a suite of four guidance documents – builds upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products,” the FDA announced in a statement released on Nov. 16.

[email protected]

The Food and Drug Administration has announced a new policy that addresses the rapid growth and development of regenerative medicine products, which include novel cellular therapies, with the aim of ensuring their safety and effectiveness.

“The framework – outlined in a suite of four guidance documents – builds upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products,” the FDA announced in a statement released on Nov. 16.

[email protected]

The Food and Drug Administration has announced a new policy that addresses the rapid growth and development of regenerative medicine products, which include novel cellular therapies, with the aim of ensuring their safety and effectiveness.

“The framework – outlined in a suite of four guidance documents – builds upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products,” the FDA announced in a statement released on Nov. 16.

[email protected]