Loncastuximab Tesirine-Ipyl Added to NCCN Guidelines for B-Cell Lymphomas

Jay Feingold, MD, PhD

The recently FDA-approved loncastuximab tesirine-lpyl (Zynlonta) has been added to the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for B-cell lymphomas, according to ADC Therapeutics SA.¹

Specifically, the CD19-dirtected antibody and alkylating agent conjugate is now included as a category 2A designation as a therapeutic option for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following 2 or more lines of systemic therapy.

“We are pleased to learn that less than 2 weeks after accelerated FDA approval, [loncastuximab tesirine] was added to the NCCN treatment guidelines with a category 2A recommendation,” Chris Martin, chief executive officer of ADC Therapeutics, stated in the press release. “Inclusion in the NCCN treatment guidelines highlights the high unmet medical need for differentiated, targeted therapy in relapsed and refractory DLBCL.”

In April 2021, loncastuximab tesirine was granted approval by the FDA for use in patients with relapsed or refractory large B-cell lymphoma following 2 or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma based on data from the phase 2 LOTIS-2 study (NCT03589469).

Data indicated that the agent induced an objective response rate (ORR) of 48.3% in patients with relapsed/refractory disease who had previously received 2 or more lines of systemic therapy; this included a 24.1% complete response (CR) rate.²

The multicenter, open-label, single-arm LOTIS-2 trial examined the safety and efficacy of loncastuximab tesirine in patients with relapsed/refractory DLBCL who had previously received 2 or more lines of systemic therapy. Notably, all participants had received a median of 3 lines of prior therapy.

Patients received the agent via a 30-minute infusion at a dose of 150 μg/kg, once every 3 weeks for the first 2 cycles of treatment. Subsequently, the drug was given at a dose of 75 μg/kg. Treatment was administered for 1 year, or until progressive disease, intolerable toxicity, or if other discontinuation criteria were met.

A total of 145 patients had been enrolled to the trial by the April 6, 2020 data cutoff. Participants had received a mean of 4.3 cycles of loncastuximab tesirine (range, 1-15). Additional findings presented during the 2020 European Hematology Association Congress demonstrated that the agent elicited an ORR of 37.9% in patients who were refractory to their first-line therapy. In patients who were refractory to their last line of prior treatment, the ORR with the agent was 36.9%. The median duration of response with loncastuximab tesirine was 10.25 months.

The most frequently reported grade 3 or higher treatment-emergent adverse effects experienced with the antibody-drug conjugate included neutropenia (25.5%) with low incidence of febrile neutropenia (3.4%), thrombocytopenia (17.9%), increased gamma-glutamyl transferase (16.6%), and anemia (10.3%).

In a phase 1/2 trial, loncastuximab tesirine is also being evaluated in combination with ibrutinib (Imbruvica) as a treatment for patients with relapsed/refractory DLBCL or mantle cell lymphoma (MCL).³

A total of 23 patients with DLBCL and 2 patients with MCL were enrolled to the trial as of April 2020. In the dose-escalation portion of the research, participants were given a median of 2 cycles of treatment with loncastuximab tesirine at a dose of 60 μg/kg (n = 19) or 90 μg/kg (n = 6) for a median duration of 42 days (range, 1-379).

The regimens were delivered intravenously via 30-minute infusions utilizing the standard 3+3 dose-escalation design. Participants were given the ADC every 3 weeks for the first 2 doses, followed by concurrent ibrutinib at a daily dose of 560 mg for up to 1 year. The combination resulted in an ORR of 66.7%, which included 9 CRs and 3 partial responses.

Moreover, the combination of loncastuximab tesirine and rituximab (Rituxan) is being compared with chemoimmunotherapy in patients with relapsed/refractory DLBCL in the phase 3 confirmatory LOTIS 5 trial (NCT04384484).⁴

“The rapid inclusion of [loncastuximab tesirine] in the NCCN guidelines reinforces our work on behalf of patients who have been heavily pretreated and have difficult-to-treat disease,” Jay Feingold, MD, PhD, senior vice president and chief medical officer at ADC Therapeutics, added in the release. “Importantly, there is a broad range of pretreated patients needing new therapies, including those who are transplant eligible and ineligible, and patients who previously received stem cell transplant or CAR T-cell therapy.”

References

1. ADC Therapeutics’ ZYNLONTA (loncastuximab tesirine-lpyl) added to National Comprehensive Cancer Network clinical practice guidelines in oncology for B-cell lymphomas. News release. May 5, 2021. Accessed May 6, 2021. https://bit.ly/3b7srYg
2. ADC Therapeutics SA (ADCT) Announces FDA Approval of ZYNLONTA™ (loncastuximab tesirine-lpyl) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. News release. ADC Therapeutics. April 23, 2021. Accessed May 6, 2021. https://bit.ly/3tI7330
3. ADC Therapeutics announces maturing data from pivotal phase 2 clinical trial and phase 1/2 combination clinical trial of loncastuximab tesirine (Lonca) in patients with relapsed or refractory diffuse large B-cell lymphoma. News release. ADC Therapeutics SA. June 12, 2020. Accessed May 6, 2021. https://bwnews.pr/33Q1mnX.
4. Study to evaluate loncastuximab tesirine with rituximab versus immunochemotherapy in participants with relapsed or refractory diffuse large B-cell lymphoma. Clinicaltrials.gov. Updated September 17, 2020. Accessed May 6, 2021. https://clinicaltrials.gov/ct2/show/NCT04384484.