MRD-negative status signals better outcomes in CAR T–treated ALL

 

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

 

Most of the MRD-negative patients who relapsed did so within the first 6 months, an observation that led investigators to consider whether factors exist that could predict better outcomes.

In a multivariate analysis, they found three variables associated with disease free survival: higher LDH prior to lymphodepletion (hazard ratio, 1.39), along with higher platelet count prior to lymphodepletion and incorporation of fludarabine into the regimen, with hazard ratios of 0.65 and 0.34, respectively.

Using those three characteristics, investigators grouped patients as “good risk” if they had normal LDH, platelet count at or above 100 prior to lymphodepletion that included fludarabine. The 24-month disease-free survival for good-risk patients was 78%, and overall survival was 86%.

The role of allogeneic HSCT after ALL patients achieved MRD-negative complete remission with CAR T-cell therapy was one of the “major questions in the field,” Dr. Hay said.

 

In this analysis, Dr. Hay and colleagues found that patients who underwent transplant in MRD-negative complete remission had a 24-month disease free survival and overall survival of 61% and 72%, respectively, both of which were significantly higher than in patients with MRD-negative complete remission who had no transplant.

The disease-free survival benefit was not specific to the good-risk group, according to Dr. Hay, who said an interaction test demonstrated no significant interaction between risk group and allogeneic HSCT after CAR T-cell infusion (P = 0.53).

“This is a very important finding that should be further [studied] in an appropriately designed clinical trial,” Dr. Hay said during an oral presentation of the study results.

Dr. Hay and several coauthors reported financial disclosures related to Juno Therapeutics. Other disclosures reported by study coauthors included Cell Medica, Celgene, Eureka Therapeutics, Genentech/Roche, Gilead Sciences, Kite Pharma, Novartis, and others.

SOURCE: Hay KA. ASCO 2018, Abstract 7005.

 

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

 

Most of the MRD-negative patients who relapsed did so within the first 6 months, an observation that led investigators to consider whether factors exist that could predict better outcomes.

In a multivariate analysis, they found three variables associated with disease free survival: higher LDH prior to lymphodepletion (hazard ratio, 1.39), along with higher platelet count prior to lymphodepletion and incorporation of fludarabine into the regimen, with hazard ratios of 0.65 and 0.34, respectively.

Using those three characteristics, investigators grouped patients as “good risk” if they had normal LDH, platelet count at or above 100 prior to lymphodepletion that included fludarabine. The 24-month disease-free survival for good-risk patients was 78%, and overall survival was 86%.

The role of allogeneic HSCT after ALL patients achieved MRD-negative complete remission with CAR T-cell therapy was one of the “major questions in the field,” Dr. Hay said.

 

In this analysis, Dr. Hay and colleagues found that patients who underwent transplant in MRD-negative complete remission had a 24-month disease free survival and overall survival of 61% and 72%, respectively, both of which were significantly higher than in patients with MRD-negative complete remission who had no transplant.

The disease-free survival benefit was not specific to the good-risk group, according to Dr. Hay, who said an interaction test demonstrated no significant interaction between risk group and allogeneic HSCT after CAR T-cell infusion (P = 0.53).

“This is a very important finding that should be further [studied] in an appropriately designed clinical trial,” Dr. Hay said during an oral presentation of the study results.

Dr. Hay and several coauthors reported financial disclosures related to Juno Therapeutics. Other disclosures reported by study coauthors included Cell Medica, Celgene, Eureka Therapeutics, Genentech/Roche, Gilead Sciences, Kite Pharma, Novartis, and others.

SOURCE: Hay KA. ASCO 2018, Abstract 7005.

 

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

 

Most of the MRD-negative patients who relapsed did so within the first 6 months, an observation that led investigators to consider whether factors exist that could predict better outcomes.

In a multivariate analysis, they found three variables associated with disease free survival: higher LDH prior to lymphodepletion (hazard ratio, 1.39), along with higher platelet count prior to lymphodepletion and incorporation of fludarabine into the regimen, with hazard ratios of 0.65 and 0.34, respectively.

Using those three characteristics, investigators grouped patients as “good risk” if they had normal LDH, platelet count at or above 100 prior to lymphodepletion that included fludarabine. The 24-month disease-free survival for good-risk patients was 78%, and overall survival was 86%.

The role of allogeneic HSCT after ALL patients achieved MRD-negative complete remission with CAR T-cell therapy was one of the “major questions in the field,” Dr. Hay said.

 

In this analysis, Dr. Hay and colleagues found that patients who underwent transplant in MRD-negative complete remission had a 24-month disease free survival and overall survival of 61% and 72%, respectively, both of which were significantly higher than in patients with MRD-negative complete remission who had no transplant.

The disease-free survival benefit was not specific to the good-risk group, according to Dr. Hay, who said an interaction test demonstrated no significant interaction between risk group and allogeneic HSCT after CAR T-cell infusion (P = 0.53).

“This is a very important finding that should be further [studied] in an appropriately designed clinical trial,” Dr. Hay said during an oral presentation of the study results.

Dr. Hay and several coauthors reported financial disclosures related to Juno Therapeutics. Other disclosures reported by study coauthors included Cell Medica, Celgene, Eureka Therapeutics, Genentech/Roche, Gilead Sciences, Kite Pharma, Novartis, and others.

SOURCE: Hay KA. ASCO 2018, Abstract 7005.