Anti-PD1 monoclonal antibodies before and after allogeneic hematopoietic cell transplantation for relapsed or refractory Hodgkin lymphoma

The study evaluated outcomes of anti-programmed cell death-1 monoclonal antibodies (anti-PD-1-mAbs or APMs) before and after allogeneic hematopoietic cell transplantation (alloHCT) for patients with relapsed/refractory Hodgkin lymphoma (r/r-HL). The authors found that patients receiving APMs before alloHCT had frequent immune-related complications and favorable survival.

Treatment outcomes in patients with r/r-HL are poor. Relapsed refers to the return of cancer and refractory means when cancer is unresponsive therapy. APMs such as nivolumab (Opdivo) or pembrolizumab (Keytruda) are immunotherapy drugs that kill cancer cells by blocking PD1 proteins. This heightens the immune response against the cancer. They showed effectiveness in treating r/r-HL.

AlloHCT is performed by transplanting healthy stem cells from donors. It is recommended for patients with r/r-HL whose cancer relapses after APM therapy. However, the safety and effectiveness of this therapy before or after alloHCT are not clarified.

The study analyzed past records of 45 adult patients with r/r-HL. APMs were given to 25 patients before alloHCT (PRE group) and to 20 patients after alloHCT (POST group). Patients from PRE-group were followed-up for 319 days from alloHCT on average. Those from the POST group were followed up for an average of 1717 days after alloHCT.

Participants in the PRE group developed frequent immune-related complications (IRCs) such as fever, engraftment syndrome (ES), and graft-vs-host-disease (GvHD). ES is characterized by fever, skin rash, weight gain, liver, and kidney dysfunction. GvHD occurs when immune cells from the donor’s bone marrow attack the patient’s body.

60% of PRE-group patients experienced fever without infections after lloaHCT. 6 of these patients developed ES. Overall, 68% of patients experienced short-term GvHD (GvHD). The risk of facing severe short-term GvHD after 100 days of alloHCT was 0% in patients who received post-transplant cyclophosphamide (PTCy; Cytoxan). This was compared to 23.5% in patients who did not receive PTCy. 

80% of PRE-group patients achieved complete remission (CR; the disappearance of the cancer) and 4% had stable disease (SD). The chance of overall survival (OS) at 1 year was 81.3%. 63.7% in the PRE-group were alive at 1 year without cancer worsening.

In the POST group, APMs were started after an average of 589 days after alloHCT. GvHD occurred in 50% of patients and 55% experienced IRCs. A CR was recorded in 40% and SD in 20% of patients in the POST-group. 35% of patients had a partial response (shrinkage of the cancer). Chances of OS at 1 year were 89.7% in the POST group. 52.6%.of patients were alive at 1 year without cancer worsening.

The study concluded that IRCs were frequent and survival was favorable in patients with r/r-HL receiving APMs before alloHCT. The authors suggest that PTCy treatment may be effective in these patients.

The study was conducted on Japanese patients only. It also could not make a definite conclusion about APMs’ effectiveness in r/r-HL before or after alloHCT.