Immunotherapy may improve HSCT outcomes

VALENCIA, SPAIN—Results of a phase 2 trial suggest a personalized T-cell immunotherapy may improve outcomes in patients undergoing T-cell-depleted haploidentical hematopoietic stem cell transplant (HSCT).

Patients who received the therapy, ATIR101, after HSCT had significant improvements in transplant-related mortality (TRM) and overall survival (OS) when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.

None of the patients who received ATIR101 developed grade 3-4 graft-versus-host disease (GVHD), despite the fact that they had not received any prophylactic immunosuppressants. Still, there were a few cases of grade 2 GVHD reported.

Denis-Claude Roy, MD, of the University of Montreal in Québec, Canada, presented the results of this trial at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation (abstract O042*). The trial was sponsored by Kiadis Pharma, the company developing ATIR101.

Patients and treatment

The trial included 23 leukemia patients with a median age of 41 (range, 21-64). They were eligible for an allogeneic HSCT but could not find a matching donor in time. Sixteen patients had acute myeloid leukemia, and 7 had acute lymphoblastic leukemia.

All patients were in complete remission (CR) at the time of the HSCT. Fifteen were in CR1, and 8 were in CR2/3. The majority of patients (57%) had a poor prognosis based on their disease risk index and cytogenetic profile.

A myeloablative conditioning regimen was used, which consisted of total body irradiation (1200 cGy; n=11) or melphalan (120 mg/m²; n=12), along with thiotepa (10 mg/kg), fludarabine (30 mg/m² x 5d), and anti-thymocyte globulin (2.5 mg/kg x 4d).

Patients then received a CD34⁺ selected graft from a haploidentical donor, containing 11 x 10⁶ CD34⁺ cells/kg (range, 4.7-24.4) and 0.29 x 10⁴ CD3⁺ cells/kg (range, 0-1.8).

The patients achieved neutrophil and platelet engraftment at a median of 12 days post-HSCT (range, 8-34 and 9-35, respectively). They did not receive any post-transplant GVHD prophylaxis.

At a median of 28 days post-transplant (range, 28-73), ATIR101 was infused, at a fixed dose of 2 x 10⁶ CD3⁺ cells/kg.

ATIR101 is a personalized T-cell immunotherapy based on a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.

Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with a compound known as TH9402, which is selectively retained in activated T cells. Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.

Primary endpoint: TRM

The median follow-up, on March 24, 2016, was 414 days (range, 110-742) post-HSCT. At that point, all patients were beyond 6 months post-HSCT. This allowed for assessment of the primary endpoint, which is TRM at 6 months.

Three cases of TRM were reported, for a rate of 13%. In all cases, the cause of death was an infection.

The researchers compared these results to those in a historic control group. It consisted of 35 patients who matched the inclusion and exclusion criteria of this trial and underwent a similar HSCT procedure from haploidentical family members but without the addition of ATIR101.

TRM was significantly lower (P=0.005) in patients who received ATIR101 after a T-cell-depleted haploidentical transplant than in the historical controls. The 6-month TRM for HSCT + ATIR101 was 13%, compared to 37% for HSCT only.

Relapse and survival

Two patients experienced disease relapse within the first 12 months after HSCT—at days 61 and 90. And 1 patient died from disease relapse within the first 6 months.

The researchers said the low rates of relapse and TRM translated into significantly improved OS for patients undergoing HSCT + ATIR101 compared to the historical controls.

Based on Kaplan-Meier estimates, the 1-year OS was 64% in the HSCT + ATIR101 group and 20% in the historical control group (P=0.0026).

GVHD

None of the patients in this trial (0/23) developed grade 3-4 GVHD upon infusion of ATIR101.

However, 3 cases of grade 2 acute GVHD were reported. One case occurred before ATIR101 infusion, and the other 2 cases had a delayed onset, at day 173 and day 247 post-HSCT (145 and 219 days post-ATIR101 infusion).

In the patient who developed GVHD before ATIR101 infusion, GVHD resolved quickly. The patient then received ATIR101 and did not experience any further GVHD.

“With this latest data, we can confirm the safety of ATIR101, without any incidents of grade 3-4 GVHD, significant reduction in transplant-related mortality, low relapse rates, and very good event-free survival, which we believe confirms the efficiency of photodepletion-based elimination of allo-reactive T cells,” Dr Roy said.

“Indeed, the data of patients receiving transplants with a haploidentical donor and an ATIR101 infusion are very similar to those from patients with a matched donor. As a doctor, I am very excited about this development and its potential to change patient fates.”

Dr Roy and his colleagues will continue to follow patients in this trial to collect further long-term outcome data.

Kiadis Pharma is planning to proceed with the development of ATIR101 as an adjunctive immuno-therapeutic treatment to a haploidentical HSCT for patients with acute leukemia, initiating a randomized phase 3 trial in the second half of 2016.

*Information in the abstract differs from that presented at the meeting.

VALENCIA, SPAIN—Results of a phase 2 trial suggest a personalized T-cell immunotherapy may improve outcomes in patients undergoing T-cell-depleted haploidentical hematopoietic stem cell transplant (HSCT).

Patients who received the therapy, ATIR101, after HSCT had significant improvements in transplant-related mortality (TRM) and overall survival (OS) when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.

None of the patients who received ATIR101 developed grade 3-4 graft-versus-host disease (GVHD), despite the fact that they had not received any prophylactic immunosuppressants. Still, there were a few cases of grade 2 GVHD reported.

Denis-Claude Roy, MD, of the University of Montreal in Québec, Canada, presented the results of this trial at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation (abstract O042*). The trial was sponsored by Kiadis Pharma, the company developing ATIR101.

Patients and treatment

The trial included 23 leukemia patients with a median age of 41 (range, 21-64). They were eligible for an allogeneic HSCT but could not find a matching donor in time. Sixteen patients had acute myeloid leukemia, and 7 had acute lymphoblastic leukemia.

All patients were in complete remission (CR) at the time of the HSCT. Fifteen were in CR1, and 8 were in CR2/3. The majority of patients (57%) had a poor prognosis based on their disease risk index and cytogenetic profile.

A myeloablative conditioning regimen was used, which consisted of total body irradiation (1200 cGy; n=11) or melphalan (120 mg/m²; n=12), along with thiotepa (10 mg/kg), fludarabine (30 mg/m² x 5d), and anti-thymocyte globulin (2.5 mg/kg x 4d).

Patients then received a CD34⁺ selected graft from a haploidentical donor, containing 11 x 10⁶ CD34⁺ cells/kg (range, 4.7-24.4) and 0.29 x 10⁴ CD3⁺ cells/kg (range, 0-1.8).

The patients achieved neutrophil and platelet engraftment at a median of 12 days post-HSCT (range, 8-34 and 9-35, respectively). They did not receive any post-transplant GVHD prophylaxis.

At a median of 28 days post-transplant (range, 28-73), ATIR101 was infused, at a fixed dose of 2 x 10⁶ CD3⁺ cells/kg.

ATIR101 is a personalized T-cell immunotherapy based on a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.

Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with a compound known as TH9402, which is selectively retained in activated T cells. Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.

Primary endpoint: TRM

The median follow-up, on March 24, 2016, was 414 days (range, 110-742) post-HSCT. At that point, all patients were beyond 6 months post-HSCT. This allowed for assessment of the primary endpoint, which is TRM at 6 months.

Three cases of TRM were reported, for a rate of 13%. In all cases, the cause of death was an infection.

The researchers compared these results to those in a historic control group. It consisted of 35 patients who matched the inclusion and exclusion criteria of this trial and underwent a similar HSCT procedure from haploidentical family members but without the addition of ATIR101.

TRM was significantly lower (P=0.005) in patients who received ATIR101 after a T-cell-depleted haploidentical transplant than in the historical controls. The 6-month TRM for HSCT + ATIR101 was 13%, compared to 37% for HSCT only.

Relapse and survival

Two patients experienced disease relapse within the first 12 months after HSCT—at days 61 and 90. And 1 patient died from disease relapse within the first 6 months.

The researchers said the low rates of relapse and TRM translated into significantly improved OS for patients undergoing HSCT + ATIR101 compared to the historical controls.

Based on Kaplan-Meier estimates, the 1-year OS was 64% in the HSCT + ATIR101 group and 20% in the historical control group (P=0.0026).

GVHD

None of the patients in this trial (0/23) developed grade 3-4 GVHD upon infusion of ATIR101.

However, 3 cases of grade 2 acute GVHD were reported. One case occurred before ATIR101 infusion, and the other 2 cases had a delayed onset, at day 173 and day 247 post-HSCT (145 and 219 days post-ATIR101 infusion).

In the patient who developed GVHD before ATIR101 infusion, GVHD resolved quickly. The patient then received ATIR101 and did not experience any further GVHD.

“With this latest data, we can confirm the safety of ATIR101, without any incidents of grade 3-4 GVHD, significant reduction in transplant-related mortality, low relapse rates, and very good event-free survival, which we believe confirms the efficiency of photodepletion-based elimination of allo-reactive T cells,” Dr Roy said.

“Indeed, the data of patients receiving transplants with a haploidentical donor and an ATIR101 infusion are very similar to those from patients with a matched donor. As a doctor, I am very excited about this development and its potential to change patient fates.”

Dr Roy and his colleagues will continue to follow patients in this trial to collect further long-term outcome data.

Kiadis Pharma is planning to proceed with the development of ATIR101 as an adjunctive immuno-therapeutic treatment to a haploidentical HSCT for patients with acute leukemia, initiating a randomized phase 3 trial in the second half of 2016.

*Information in the abstract differs from that presented at the meeting.

VALENCIA, SPAIN—Results of a phase 2 trial suggest a personalized T-cell immunotherapy may improve outcomes in patients undergoing T-cell-depleted haploidentical hematopoietic stem cell transplant (HSCT).

Patients who received the therapy, ATIR101, after HSCT had significant improvements in transplant-related mortality (TRM) and overall survival (OS) when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.

None of the patients who received ATIR101 developed grade 3-4 graft-versus-host disease (GVHD), despite the fact that they had not received any prophylactic immunosuppressants. Still, there were a few cases of grade 2 GVHD reported.

Denis-Claude Roy, MD, of the University of Montreal in Québec, Canada, presented the results of this trial at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation (abstract O042*). The trial was sponsored by Kiadis Pharma, the company developing ATIR101.

Patients and treatment

The trial included 23 leukemia patients with a median age of 41 (range, 21-64). They were eligible for an allogeneic HSCT but could not find a matching donor in time. Sixteen patients had acute myeloid leukemia, and 7 had acute lymphoblastic leukemia.

All patients were in complete remission (CR) at the time of the HSCT. Fifteen were in CR1, and 8 were in CR2/3. The majority of patients (57%) had a poor prognosis based on their disease risk index and cytogenetic profile.

A myeloablative conditioning regimen was used, which consisted of total body irradiation (1200 cGy; n=11) or melphalan (120 mg/m²; n=12), along with thiotepa (10 mg/kg), fludarabine (30 mg/m² x 5d), and anti-thymocyte globulin (2.5 mg/kg x 4d).

Patients then received a CD34⁺ selected graft from a haploidentical donor, containing 11 x 10⁶ CD34⁺ cells/kg (range, 4.7-24.4) and 0.29 x 10⁴ CD3⁺ cells/kg (range, 0-1.8).

The patients achieved neutrophil and platelet engraftment at a median of 12 days post-HSCT (range, 8-34 and 9-35, respectively). They did not receive any post-transplant GVHD prophylaxis.

At a median of 28 days post-transplant (range, 28-73), ATIR101 was infused, at a fixed dose of 2 x 10⁶ CD3⁺ cells/kg.

ATIR101 is a personalized T-cell immunotherapy based on a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.

Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with a compound known as TH9402, which is selectively retained in activated T cells. Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.

Primary endpoint: TRM

The median follow-up, on March 24, 2016, was 414 days (range, 110-742) post-HSCT. At that point, all patients were beyond 6 months post-HSCT. This allowed for assessment of the primary endpoint, which is TRM at 6 months.

Three cases of TRM were reported, for a rate of 13%. In all cases, the cause of death was an infection.

The researchers compared these results to those in a historic control group. It consisted of 35 patients who matched the inclusion and exclusion criteria of this trial and underwent a similar HSCT procedure from haploidentical family members but without the addition of ATIR101.

TRM was significantly lower (P=0.005) in patients who received ATIR101 after a T-cell-depleted haploidentical transplant than in the historical controls. The 6-month TRM for HSCT + ATIR101 was 13%, compared to 37% for HSCT only.

Relapse and survival

Two patients experienced disease relapse within the first 12 months after HSCT—at days 61 and 90. And 1 patient died from disease relapse within the first 6 months.

The researchers said the low rates of relapse and TRM translated into significantly improved OS for patients undergoing HSCT + ATIR101 compared to the historical controls.

Based on Kaplan-Meier estimates, the 1-year OS was 64% in the HSCT + ATIR101 group and 20% in the historical control group (P=0.0026).

GVHD

None of the patients in this trial (0/23) developed grade 3-4 GVHD upon infusion of ATIR101.

However, 3 cases of grade 2 acute GVHD were reported. One case occurred before ATIR101 infusion, and the other 2 cases had a delayed onset, at day 173 and day 247 post-HSCT (145 and 219 days post-ATIR101 infusion).

In the patient who developed GVHD before ATIR101 infusion, GVHD resolved quickly. The patient then received ATIR101 and did not experience any further GVHD.

“With this latest data, we can confirm the safety of ATIR101, without any incidents of grade 3-4 GVHD, significant reduction in transplant-related mortality, low relapse rates, and very good event-free survival, which we believe confirms the efficiency of photodepletion-based elimination of allo-reactive T cells,” Dr Roy said.

“Indeed, the data of patients receiving transplants with a haploidentical donor and an ATIR101 infusion are very similar to those from patients with a matched donor. As a doctor, I am very excited about this development and its potential to change patient fates.”

Dr Roy and his colleagues will continue to follow patients in this trial to collect further long-term outcome data.

Kiadis Pharma is planning to proceed with the development of ATIR101 as an adjunctive immuno-therapeutic treatment to a haploidentical HSCT for patients with acute leukemia, initiating a randomized phase 3 trial in the second half of 2016.

*Information in the abstract differs from that presented at the meeting.