Kami Maddocks, MD

Kami Maddocks, MD, an associate professor of clinical internal medicine, Division of Hematology, at The Ohio State University Comprehensive Cancer Center–James, discusses potential treatments in follicular lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy looks promising in follicular lymphoma and there may be a specific group of these patients who benefit the most from this treatment, according to Maddocks. There are also newer bispecific antibodies that been investigated for relapsed lymphoma in general, and these studies have included patients with follicular lymphoma as well. Although bispecific agents are in early stages of their studies, they appear promising for patients, with less toxicity and easier administration access. She feels this is exciting option for physicians treating patients with follicular lymphoma.

Maddocks says other potential therapies for the future of the follicular lymphoma landscape include antibody drug conjugates (ADCs), which have data in large cell lymphomas. ADCs already have approvals in Hodgkin lymphoma and other proliferative diseases. Tafasitamab (Monjuvi), a single-agent CD19 anitbody, was recently approved in large cell lymphomas in combination with lenalidomide (Revlimid) and will most likely be evaluated further in follicular lymphoma.

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Kami Maddocks, MD, discusses potential treatments in follicular lymphoma.

Exploring Potential Agents in Development for Follicular Lymphoma

Kami J. Maddocks, MD, associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses the role of tafasitamab (Monjuvi) and lenalidomide (Revlimid) following the approval of this agent as treatment of patients with relapsed/refractory diffuse large B-cell lymphoma.

For patients who are ineligible for salvage chemotherapy followed by transplant, this combination was approved for the treatment of patients after first relapse. Historically, physicians would provide some sort of palliative chemotherapy in this setting if the patient was a candidate and was pursuing therapy or had consideration of clinical trial, but this is the only approved agent in this setting, Maddocks says.

The overall response rate in the phase 2 study that led to the combination’s approval was 60% with a complete response rate of 40%. The median progression-free survival was a little over 1 year, and the median overall survival was not reached in the initial dataset. With further follow-up, though, Maddocks says the median duration of response was nearly 3 years. This is an impressive finding, that patients achieve durable responses with the combination.

Kami J. Maddocks, MD, discusses the role of tafasitamab and lenalidomide following the approval of this agent as treatment of patients with relapsed/refractory diffuse large B-cell lymphoma.

Tafasitamab Plus Lenalidomide Approval Generates Excitement for Second-Line DLBCL

Kami J. Maddocks, MD, associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses the use of Bruton’s tyrosine kinase (BTK) inhibitors in patients with B-cell malignancies and how that may change in the future to provide more treatment options for these patients.

BTK inhibitors are currently used as single-agent therapies and are continued indefinitely if patients are tolerating treatment and having a good response. Some questions for this type of treatment include how well it would work as a frontline therapy and if combinations of BTK inhibitors could produce deeper remissions, according to Maddocks.

Maddocks says another question is whether treatments could allow for limited therapies. This means if a patient receives multiple drugs over the course of 2 to 3 years and they are able to achieve deep remissions or minimal residual disease negative remissions, will that patient be able to stop these therapies after a shorter amount of time instead of being on treatment indefinitely? The patient stopping therapy after a while helps decrease long-term toxicity and cost. A follow-up question is whether patients could be retreated with these therapies after stopping treatment and relapsing a few years down the line.

In mantle cell lymphoma, where BTK inhibitors are used in the relapsed setting, Maddocks asks whether it could be moved up to the frontline setting to improve outcomes in those patients.

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Kami J. Maddocks, MD, discusses the use of Bruton’s tyrosine kinase inhibitors in patients with B-cell malignancies and how that may change in the future to provide more treatment options for these patients.

Exploring Questions Remaining for BTK Inhibitors and B-Cell Malignancies

 There are ongoing gaps in the care of mantle cell lymphoma, and there are a few big areas of study. While the BTK inhibitors are very effective, there are still more patients who are going to relapse from their disease. We are trying to prolong these remission durations and deepen the remission durations with single-agent BTK therapy, so there’s a lot of interest going into trials with multiagent, including multiple oral agents. Adding the oral BCL2 inhibitor venetoclax to ibrutinib has shown some promising results. Studies are looking at adding an oral immunomodulator, like lenalidomide, and a number of these different oral BTK inhibitors to really try to prolong and deepen the remission duration.

The other area of interest is in patients with bad prognostic disease: patients with blastoid histology…patients with 

 mutations who do poorly in general. Even with ibrutinib therapy, patients had either worse progression-free survival or the 

-mutated patients have worse overall responses. Treating this high-risk population of patients is of high interest. Probably the most exciting ongoing thing in mantle cell right now is results of the recent ZUMA-2 study, which was anti-CD19 chimeric antigen receptor CAR T-cell therapy in relapsed/refractory mantle cell lymphoma patients.

All patients on that trial had been treated with prior BTK therapy, and these had gone up through progression or intolerance to those, and they showed very high response rate. Almost everybody on the trial responded to therapy. Of the 97% overall response rate, 67% of patients exceeded complete remission.

There is toxicity associated with this similar to what there is in large-cell and follicular lymphoma, with neurotoxicity and cytokine release. But there are very promising results, unprecedented results in a population of patients with very poor progression-free survival and overall survival. One of the most exciting things is that we’ll be looking forward to that approval and then CAR T cells that can be even better with less toxicity.

Case: A 76-Year-Old Woman with High Risk Mantle Cell Lymphoma

A 76-year-old woman presented with a 2-month history of occasional night sweats, intermittent fatigue and decreased appetite

PMH: DM, medically controlled; GERD controlled on OTC medication

PE: bilateral cervical lymphadenopathy, splenomegaly



LDH 405 U/I, ANC 3200/mm3, beta-2-microglobulin 4.1 µg/L, leukocytes, 5.42 X 109/L, hemoglobin 9.1 gm/dL

Immunocytochemistry: cyclin D1+, CD5+, CD20+, CD43+, CD10-, CD23-

Bone marrow biopsy positive for lymphoid cells with cyclin D1

PET/CT scan showed widespread lymphadenopathy including inguinal node (5.1 cm) and splenomegaly

Ann Arbor stage IV; MIPI score 6.4; ECOG PS 0



She was started on bendamustine + rituximab

At 18 months the patient had clinical disease relapse, including an unintentional 7-lb weight loss

She was started on ibrutinib 560 mg PO qDay

Imaging at 10-week follow-up showed substantial decrease in disease burden

Kami Maddocks, MD | Authors

Articles

Exploring Potential Agents in Development for Follicular Lymphoma

Tafasitamab Plus Lenalidomide Approval Generates Excitement for Second-Line DLBCL

Exploring Questions Remaining for BTK Inhibitors and B-Cell Malignancies

Unmet Needs and Future of R/R Mantle Cell Lymphoma