Juan P. Alderuccio, MD, is an associate professor of medicine and clinical site disease group leader in the Lymphoma Section at Sylvester Comprehensive Cancer Center, University of Miami Health System.

Dr Alderuccio on Loncastuximab Tesirine Plus Rituximab in High-Risk R/R Follicular Lymphoma

"The primary study end point was the complete response [CR] rate at week 12 by Lugano criteria, and we observed [a 12-week] overall response rate of 97.4% with a CR rate of 66.7%. Based on this result, the study met its [primary end point].

Juan P. Alderuccio, MD, an assistant professor of clinical medicine at Sylvester Comprehensive Cancer Center, University of Miami Health System, discussed results from a phase 2, investigator-initiated, single-arm study (NCT04998669) evaluating the efficacy and safety of loncastuximab tesirine (Zynlota) in combination with rituximab (Rituxan) in patients with high-risk, relapsed/refractory follicular lymphoma.

The study’s primary end point was complete response (CR) rate at week 12 per Lugano criteria. At 12 weeks, the overall response rate (ORR) was 97.4%, and the CR rate was 66.7%. The best ORR and best CR rate at any point were 97.4% and 76.9%, respectively. The 12-month progression-free survival (PFS) rate was 94.6%, and the median PFS was not yet reached.

The safety profile of the regimen was consistent with prior studies of loncastuximab tesirine in large B-cell lymphoma, and no new safety signals were observed. Most adverse effects were grade 1 or 2, and the most common included hyperglycemia, elevated liver enzyme levels, fatigue, and rash. No unexpected toxicities were reported, and the combination was generally well tolerated.

This study highlighted the potential role of a fixed-duration regimen of loncastuximab tesirine plus rituximab as an effective therapeutic strategy in second-line and later settings for patients with follicular lymphoma, particularly those with high tumor burden and early relapse following first-line therapy, Alderuccio explained. The depth and speed of response, along with the manageable safety profile, underscored the rationale for further investigation of this antibody-drug conjugate–based regimen in broader clinical trials.

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Juan P. Alderuccio, MD, discusses data from loxcastuximab tesirine plus rituximab in high-risk, relapsed/refractory follicular lymphoma.

Dr Alderuccio on Loncastuximab Tesirine With Rituximab in R/R Follicular Lymphoma

“We observed that [51% of patients had progression of disease within 24 months and 92%] presented with a high disease burden [based on GELF criteria]. The primary study end point was the [complete response] rate, and [per Lugano criteria, at week 12], we observed [an] overall response rate of [97%] with a CR rate of [67%]. [Based on these findings, the study met its primary end point]."

Juan Pablo Alderuccio, MD, associate professor of medicine, clinical site disease group leader in the Lymphoma Section, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses findings from a phase 2, single-center, single-arm study (NCT04998669) evaluating the combination of loncastuximab tesirine-lpyl (Zynlonta) with rituximab (Rituxan) in patients with relapsed or refractory follicular lymphoma (FL) who had received at least one prior line of systemic therapy.

This study enrolled 39 patients who presented with disease progression or relapse within 24 months (POD24) after first-line treatment, one or more Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria, or second relapse, and an ECOG performance status of 0 to 2.

Among these patients, 51% had POD24 and 92% had a high disease burden with at least 1 GELF criteria. The primary end point was the complete response (CR) rate at week 12, which was achieved in 67% of patients. The 12-week overall response rate was 97%.

At the current follow-up, CRs appeared durable, with a 12-month progression-free survival (PFS) rate of 94.6% (95% CI, 79.9%-98.6%). The median PFS has not been reached. The safety profile was consistent with prior studies in large B-cell lymphoma, with no new safety concerns. The most frequently reported adverse effects were grade 1 or 2, including hyperglycemia, elevated liver enzymes, fatigue, and rash.

These findings suggest that a fixed-duration regimen of loncastuximab tesirine with rituximab is an effective second-line and later treatment option for patients with FL. Given the high CR rates, durability of responses, and manageable safety profile, further validation in larger, multicenter studies is warranted to refine patient selection and establish the role of this combination in clinical practice.

Juan Pablo Alderuccio, MD, discusses the combination of loncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma. 

Juan P. Alderuccio, MD, assistant professor of clinical medicine at Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the use of proteasome inhibitors in the frontline treatment of patients with multiple myeloma.

Proteasome inhibitors are used in the frontline setting. Typically, bortezomib (Velcade) is used in combination with cyclophosphamide or lenalidomide (Revlimid) plus dexamethasone, says Alderuccio. For some patients, bortezomib is a subcutaneous injection, he adds. In patients who are not able to receive lenalidomide or already present with neuropathy, ixazomib (Ninlaro) is an FDA-approved drug that can also be used in this setting.

In patients with high-risk features, such as 17p deletions, carfilzomib (Kyprolis) has been shown to induce deeper responses and better survival, says Alderuccio. Carfilzomib is currently approved by the FDA for use in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed/refractory disease who have received 1 to 3 lines of therapy.

Additional indications list carfilzomib as monotherapy for patients with relapsed/refractory myeloma who have received 1 or more lines of therapy. However, a pooled analysis presented at the 2018 ASH Annual Meeting showed encouraging overall response rates among high-risk, transplant-ineligible patients. Therefore, in this context, carfilzomib may be considered a suitable alternative.

Juan P. Alderuccio, MD

Articles

Dr Alderuccio on Loncastuximab Tesirine Plus Rituximab in High-Risk R/R Follicular Lymphoma

Dr Alderuccio on Loncastuximab Tesirine With Rituximab in R/R Follicular Lymphoma

Dr. Alderuccio on the Use of Proteasome Inhibitors in Frontline Myeloma