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AACR 2017: Durability of CAR T cell therapy response may depend on pretreatment disease cargo in leukaemia patients

AACR 2017: Durability of CAR T cell therapy response may depend on pretreatment disease cargo in leukaemia patients

“Adult patients with relapsed or refractory ALL have enormously poor outcomes, with the fiveyear survival rate being less than ten percent. Therefore, there is a clear need to develop effective therapy for these patients,” said Jae Park, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center (MSKCC) in Fresh York.

“To this end, we and other groups have developed and tested CD19-specific CAR T-cell therapy [19-28z CAR T-cell therapy] and have reported encouraging results, with high initial finish response rates in patients with B-ALL. However, relapses are common, even after achieving seemingly deep remission, and severe toxicities have been observed in some patients,” Park noted.

Park and colleagues, therefore, retrospectively analysed data from a prospective clinical trial that tested 19-28z CAR T-cell therapy to identify patients who benefited the most from this therapy.

All of the fifty one adult patients in this trial had relapsed or refractory B-ALL after one or more conventional multiagent chemotherapy.

The researchers measured disease cargo prior to CAR T-cell infusion in all patients and divided them into two cohorts – those who had minimal residual disease (MRD) with less than five percent blast cells in bone marrow (20 patients), and those who had morphologic disease, with five percent or more blast cells in bone marrow (31 patients).

Finish response rates in the MRD cohort and morphologic disease cohort were ninety five percent and seventy seven percent, respectively, which was not statistically different.

After a median of eighteen months of follow-up, median event-free survival and overall survival could not be computed for those in the MRD cohort (because most patients were still disease-free and alive), but they were 6.Three months and seventeen months, respectively, for those in the morphologic disease cohort.

The explore also found that long-term survival did not improve for patients in either cohort by having a hematopoietic stem cell transplant (HSCT) after CAR T-cell therapy.

“While more patients and longer follow-up will be needed to adequately address the significance of HSTC, the result of this analysis raises a question as to whether 19-28z CAR therapy can be considered as a definitive, curative therapy rather than a bridge to stem cell transplant, at least in a subset of patients,” Park noted.

“Our data suggest that incorporation of 19-28z CAR T cells at the time of MRD following firstline chemotherapy will maximise the durability of CAR T-cell mediated remissions and survival and can potentially spare these high-risk patients from HSCT, rather than waiting until they relapse morphologically and then attempting CAR T-cell therapy when it is less likely to achieve a durable long-term outcome,” Park added.

Patients from the MRD cohort fared well in terms of side effects as well, compared with those in the morphologic disease cohort.

Two of the major side effects associated with CAR T cells, cytokine release syndrome (CRS) and neurotoxicity, occurred in forty two percent and fifty eight percent of the patients, respectively, in the morphologic disease cohort, compared with five percent and fifteen percent, respectively, in those from the MRD cohort.

No case of cerebral edema was observed in either cohort of this probe, Park noted.

A limitation of the explore is that this is a retrospective analysis and the findings will need to be validated prospectively, Park said.

Further, the analysis on the influence of post-CAR allogeneic HSCT was limited by a relatively petite sample size in each cohort as the probe was not designed to specifically response or address that question.

About Author

The ONA Editor curates oncology news, views and reviews from Australia and around the world for our readers. In aggregated content, original sources will be acknowledged in the article footer.

AACR 2017: Durability of CAR T cell therapy response may depend on pretreatment disease cargo in leukaemia patients

AACR 2017: Durability of CAR T cell therapy response may depend on pretreatment disease cargo in leukaemia patients

“Adult patients with relapsed or refractory ALL have utterly poor outcomes, with the fiveyear survival rate being less than ten percent. Therefore, there is a clear need to develop effective therapy for these patients,” said Jae Park, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center (MSKCC) in Fresh York.

“To this end, we and other groups have developed and tested CD19-specific CAR T-cell therapy [19-28z CAR T-cell therapy] and have reported encouraging results, with high initial finish response rates in patients with B-ALL. However, relapses are common, even after achieving seemingly deep remission, and severe toxicities have been observed in some patients,” Park noted.

Park and colleagues, therefore, retrospectively analysed data from a prospective clinical trial that tested 19-28z CAR T-cell therapy to identify patients who benefited the most from this therapy.

All of the fifty one adult patients in this trial had relapsed or refractory B-ALL after one or more conventional multiagent chemotherapy.

The researchers measured disease cargo prior to CAR T-cell infusion in all patients and divided them into two cohorts – those who had minimal residual disease (MRD) with less than five percent blast cells in bone marrow (20 patients), and those who had morphologic disease, with five percent or more blast cells in bone marrow (31 patients).

Accomplish response rates in the MRD cohort and morphologic disease cohort were ninety five percent and seventy seven percent, respectively, which was not statistically different.

After a median of eighteen months of follow-up, median event-free survival and overall survival could not be computed for those in the MRD cohort (because most patients were still disease-free and alive), but they were 6.Three months and seventeen months, respectively, for those in the morphologic disease cohort.

The probe also found that long-term survival did not improve for patients in either cohort by having a hematopoietic stem cell transplant (HSCT) after CAR T-cell therapy.

“While more patients and longer follow-up will be needed to adequately address the significance of HSTC, the result of this analysis raises a question as to whether 19-28z CAR therapy can be considered as a definitive, curative therapy rather than a bridge to stem cell transplant, at least in a subset of patients,” Park noted.

“Our data suggest that incorporation of 19-28z CAR T cells at the time of MRD following firstline chemotherapy will maximise the durability of CAR T-cell mediated remissions and survival and can potentially spare these high-risk patients from HSCT, rather than waiting until they relapse morphologically and then attempting CAR T-cell therapy when it is less likely to achieve a durable long-term outcome,” Park added.

Patients from the MRD cohort fared well in terms of side effects as well, compared with those in the morphologic disease cohort.

Two of the major side effects associated with CAR T cells, cytokine release syndrome (CRS) and neurotoxicity, occurred in forty two percent and fifty eight percent of the patients, respectively, in the morphologic disease cohort, compared with five percent and fifteen percent, respectively, in those from the MRD cohort.

No case of cerebral edema was observed in either cohort of this investigate, Park noted.

A limitation of the explore is that this is a retrospective analysis and the findings will need to be validated prospectively, Park said.

Further, the analysis on the influence of post-CAR allogeneic HSCT was limited by a relatively puny sample size in each cohort as the investigate was not designed to specifically response or address that question.

About Author

The ONA Editor curates oncology news, views and reviews from Australia and around the world for our readers. In aggregated content, original sources will be acknowledged in the article footer.

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