ADC Offers Promising Results in Relapsed or Refractory Hodgkin Lymphoma

Investigational camidanlumab tesirine led to a high response rate in heavily pretreated patients with relapsed or refractory classical Hodgkin lymphoma (HL), according to results from a phase II trial.

With a median follow-up of 10.7 months, the drug demonstrated an overall response rate (ORR) of 70.1% among 117 patients who were refractory or had relapsed after a a median of six prior treatments, including brentuximab vedotin (Adcetris) and PD-1 blockade, reported Alex F. Herrera, MD, of City of Hope Comprehensive Cancer Center in Duarte, California.

A complete response (CR) was achieved in one-third of patients, while the partial response (PR) rate was 36.8%, and 17.9% of patients achieved stable disease, he said in a presentation at the Society of Hematologic Oncology (SOHO) annual meeting.

Camidanlumab tesirine is an antibody drug conjugate comprising a human IgG1 anti-CD25 monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer.

“Several patients experienced a long-lasting treatment effect. Most responses were observed after two cycles and 15 patients who initially had a partial response ultimately had a complete response,” Herrera stated.

But adverse events (AEs) were an issue. Almost every (99%) patient in the study had a treatment-emergent AE, with skin rash the most common. The most common grade ≥3 treatment-emergent AEs were cytopenias. All-grade treatment-emergent AEs related to the PBD dimer included skin and nail reactions (74.4% of patients), hepatobiliary test abnormalities (29.1%), and edema/effusion (17.1%).

Over half of patients (56.4%) had treatment-emergent AEs leading to dose delays or reductions, while 27.4% had treatment-emergent AEs leading to discontinuation. Four patients had treatment-emergent AEs leading to death, none of which were deemed related to camidanlumab tesirine, according to Herrera and colleagues.

Immune-related AEs occurred in 32.5% of patients, with grade ≥3 AEs occurring in 10 patients. These came on after a median of about 3.5 cycles of camidanlumab tesirine, and half emerged more than 30 days after last dose, Herrera said.

Eight patients developed Guillain-Barré syndrome (GBS) or polyradiculopathy. Herrera pointed out that “there was not a clear signal for baseline characteristics that were associated with Guillain-Barré.” However, he noted that with prompt management, such as IV immunoglobulin, plasma exchange, and/or high-dose steroids, GBS resolved in four of eight patients, and decreased in severity to grade 1 in three.

Still, SOHO session moderator Alison J. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York City, commented that the agent’s activity is “quite high, and its frustrating that we see the toxicity associated with it, and its seems to be pretty unpredictable.”

“Where do you see this drug as far as in the treatment course for Hodgkin in the future?” she said.

Herrera responded that “the toxicities are real. It’s an active drug and we have a lot of patients in a tough spot, so I think [the agent] has a role — it will have to be a role that is maybe a bridge to something else, or a palliative bridge if there’s not an intention for transplant.”

“Patients will just have to be monitored carefully,” he added. “As we learn more about how to use this agent, we’ll be able to stop therapy earlier, especially since most of the responses have been early.”

Herrera explained that all but one patient in the trial had previously received brentuximab vedotin and a checkpoint inhibitor. Of the 73 patients who previously received brentuximab vedotin and checkpoint inhibition with prior haematopoietic stem cell transplant (HSCT), 74.0% achieved a response with camidanlumab tesirine (95% CI 62.4%-83.5%). This included a CR rate of 41.1%, a PR rate of 32.9%, and a stable disease rate of 17.8%.

In the 43 patients who previously got brentuximab and checkpoint inhibition without prior HSCT, the ORR with camidanlumab tesirine was 62.8% (95% CI 46.7%-77.0%), which included an 18.6% CR rate, a 44.2% PR rate, and a 18.6% stable disease rate.

Herrera also reported that the median duration of response (DOR) was 13.7 months and median PFS was 9.1 months. Patients who achieved a CR had a median DOR 14.5 months and a median PFS 15.9 months.

Fourteen patients discontinued treatment to proceed to transplant. Of the patients who received a transplant, 11 received allogeneic transplants. Of the latter, three progressed 2-5 months after transplant. Four received autologous transplants, with one progression 2 months after transplant.

The single-arm, multicenter, open-label trial enrolled patients with a pathologic diagnosis of classical HL who had relapsed disease. Patients were required to have received at least three previous lines of systemic therapy, or two or more lines of prior therapy if ineligible for HSCT. Patients had a median age 37, 62.4% were male, and 95% had an ECOG score of 0 or 1.

Camidanlumab tesirine was administered at a dose of 45 μg/kg via a 30-minute IV infusion on day 1 of each 3-week cycle for cycles 1 and 2. For cycles 3 and on, patients received the agent at a dose of 30 μg/kg for up to 1 year.