Nilanjan Ghosh, MD, PhD, director of the Lymphoma Program and a physician with Levine Cancer Institute, discusses global trials examining zanubrutinib (Brukinsa) in mantle cell lymphoma (MCL) and non-Hodgkin lymphoma (NHL).

Several studies of interest are being done with zanubrutinib, says Ghosh. For example, 2 phase 2 studies with zanubrutinib are being conducted in patients with relapsed/refractory MCL; 1 study was done in Australia which included patients with MCL and the other study was done in China, primarily in patients with MCL. The overall response rate with the agent was around 84% and the median progression-free survival was around 17 months. The most common adverse effects observed in these studies were cytopenias, rash, and infections. Hypertension was also reported, which is similar to what is reported with most BTK inhibitors, although it was less frequently reported.

Although atrial fibrillation has been reported with other BTK inhibitors, in this study, it was not reported. However, that does not mean atrial fibrillation with zanubrutinib will never occur. In this study, atrial fibrillation was also not seen within the duration of follow-up. In the pooled analysis of patients with NHL, there was also a low rate of atrial fibrillation was reported with zanubrutinib, concludes Ghosh.

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Nilanjan Ghosh, MD, PhD, discusses global trials examining zanubrutinib in mantle cell lymphoma and non-Hodgkin lymphoma.


Dr. Ghosh on Global Trials With Zanubrutinib in MCL and NHL

Nilanjan Ghosh, MD, PhD, director of the Lymphoma Program and a physician with Levine Cancer Institute, discusses the role of minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL).

Although ​MRD has been well established as a prognostic marker in CLL, there is still much to learn in terms of risk-adapted, MRD​-directed therapies, says Ghosh. Data in that regard could spotlight the actionability of MRD in CLL.

Notably, in the phase 2 CAPTIVATE trial, patients received ibrutinib ​(Imbruvica) plus ​venetoclax (Venclexta). After 12 cycles of combination therapy, patients were randomized to continued ibrutinib monotherapy or placebo based on MRD assessment, Ghosh says

Updated data are highly anticipated in the field, Ghosh concludes. 

Nilanjan Ghosh, MD, PhD, discusses the role of minimal residual disease in chronic lymphocytic leukemia.

Dr. Ghosh on the Role of MRD in CLL 

Nilanjan Ghosh, MD, PhD, director of the Lymphoma Program and a physician with Levine Cancer Institute, discusses the utility of lisocabtagene maraleucel (liso-cel) in relapsed/refractory non-Hodgkin lymphoma (NHL).

Currently, liso-cel has been examined in the phase 1 TRANSCEND-NHL-001 study, in patients with aggressive B-cell lymphomas which were relapsed/refractory after 2 prior lines of therapy. In this patient population, liso-cel demonstrated very good efficacy and fewer toxicities. Although these are not randomized comparisons, lower rates of cytokine release syndrome (CRS) and neurotoxicity have been observed with liso-cel in relation to other products.

The composition of liso-cel is different from other CD19-directed CAR T-cell therapy products in that it consists of an equal proportion of CD8-positive and CD4-positive CAR T cells. It also uses 4-1BB costimulatory domain, but not CD28, so that may be one of the reasons why less CRS and neurotoxicity is observed.

Knowing that liso-cel has a lower toxicity profile, but good efficacy makes it an attractive agent for earlier lines of therapy, as well as a treatment option for a sicker group of patients who would have been poor candidates for autologous transplant, concludes Ghosh.

Nilanjan Ghosh, MD, PhD, discusses the utility of lisocabtagene maraleucel in relapsed/refractory non-Hodgkin lymphoma.

Dr. Ghosh on the Benefits of Lisocabtagene Maraleucel in Relapsed/Refractory NHL

Nilanjan Ghosh, MD, PhD, director, Lymphoma Program, physician, Levine Cancer Institute, discusses the safety results from the phase 2 PILOT study with lisocabtagene maraleucel (liso-cel) in non-Hodgkin lymphoma (NHL).

2020 European Hematology Association Congress

, interim data from the ongoing study showed that liso-cel elicited similar efficacy and safety as second-line therapy versus third-line therapy in patients with relapsed/refractory aggressive large B-cell NHL.

Regarding safety, investigator-assessed grade 3 or greater treatment-emergent adverse effects (TEAEs) occurred in 69% of 29 treated patients.

As with all CAR T-cell therapy studies, TEAEs of special interest including cytokine release syndrome (CRS) and neurotoxicity were assessed, explains Ghosh.

CRS and neurological events were observed in 21% and 10% of patients, respectively. There were no grade 3 or 4 CRS events, while 7% of patients experienced grade 3 neurologic events. 

The median time to onset of CRS and neurologic events was 5 days and 8 days, respectively.

Finally, 17% of patients received tocilizumab (Actemra) and/or dexamethasone for CRS or neurologic events, concludes Ghosh.

Nilanjan Ghosh, MD, PhD, discusses the safety results from the phase 2 PILOT study with lisocabtagene maraleucel in non-Hodgkin lymphoma.



Dr. Ghosh on Safety Results From the Phase 2 PILOT Trial in Non-Hodgkin Lymphoma

Nilanjan Ghosh, MD, PhD, director, Lymphoma Program, physician, Levine Cancer Institute, discusses efficacy results from the phase 2 PILOT trial in patients with high-risk relapsed/refractory B-cell non-Hodgkin lymphoma.

At a median follow-up of 5 months, 24 patients (89%) had achieved an objective response, says Ghosh.

​Moreover, the complete response ​(CR) rate was 56%, and 10 of 12 patients who achieved a CR with at least 1 follow-up assessment remained in CR, ​says Ghosh.

Additionally, 33% of patients had a partial response. Of these patients, 2 converted into a CR, Ghosh explains. The estimated 3- and 6-month CR rates were 63% and 53%.

Nilanjan Ghosh, MD, PhD, discusses efficacy results from the phase 2 PILOT trial in patients with high-risk relapsed/refractory B-cell non-Hodgkin lymphoma.

Dr. Ghosh on Efficacy Results from the Phase 2 PILOT trial in Non-Hodgkin Lymphoma

Nilanjan Ghosh, MD, PhD, director, Lymphoma Program, physician, Levine Cancer Institute, discusses the need to develop novel therapies in diffuse large B-cell lymphoma (DLBCL).

Up to 70% of patients with DLBCL, as well as other aggressive large B-cell lymphomas, may derive a long-term remission or cure from standard frontline chemoimmunotherapy regimens, says Ghosh.

Autologous stem cell transplant (ASCT) should be considered for chemotherapy-sensitive patients who relapse, he adds.

However, some patients who relapse are ineligible for ASCT due to poor prognostic features or comorbidities, says Ghosh. As such, novel therapies to treat patients who are chemotherapy refractory and ineligible for transplant are needed.

CAR T-cell therapies including lisocabtagene maraleucel (liso-cel) may have utility in this space, concludes Ghosh.

Nilanjan Ghosh, MD, PhD, discusses the need to develop novel therapies in diffuse large B-cell lymphoma.


Dr. Ghosh on the Need to Develop Novel Therapies in DLBCL

Nilanjan Ghosh, MD, PhD, physician, Levine Cancer Institute, discusses the role of bleomycin in the treatment of patients with classical Hodgkin lymphoma.

Ghosh says that he and many investigators are actively working on reducing bleomycin exposure or eliminating the agent completely from the frontline setting of Hodgkin lymphoma. Bleomycin can cause significant pulmonary toxicity that can be irreversible in some cases, Ghosh explains.

The recent RATHL trial randomized patients to doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) versus adriamycin, vinblastine, and dacarbazine (AVD). Ghosh says that since there was no significant difference in progression-free survival between the 2 groups, bleomycin does not need to be used in these patients. Additionally, most clinicians who are doing PET-adaptive therapy drop bleomycin after 2 cycles if the PET scan is negative.

Dr. Ghosh on the Role of Bleomycin in Hodgkin Lymphoma

Nilanjan Ghosh, MD, PhD, physician, Levine Cancer Institute, discusses frontline immunotherapy in Hodgkin lymphoma.

Currently, there are 2 checkpoint inhibitors approved for the treatment of patients with Hodgkin lymphoma. In May 2016, the FDA granted an accelerated approval to nivolumab (Opdivo) for the treatment of patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin (Adcetris). In March 2017, the FDA granted an accelerated approval to pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with classical Hodgkin lymphoma who are refractory or have relapsed after 3 or more lines of therapy.

Ghosh says that there may be a role for immunotherapy in the frontline setting. There are trials of immunotherapy currently ongoing, but there is not yet a head-to-head comparison. Trials are being planned to move PD-1 inhibitors to the frontline setting, says Ghosh, but there are no real-world data yet.

Dr. Ghosh on Frontline Immunotherapy in Hodgkin Lymphoma

Nilanjan Ghosh, MD, PhD, physician, Levine Cancer Institute, discusses the future of chimeric antigen receptor (CAR) T-cell therapy in the treatment of patients with hematologic malignancies.

There are many unanswered questions with regard to CAR T-cell therapy in hematologic malignancies, such as whether CAR T cells can be extended to other B-cell CD19-positive malignancies like mantle cell lymphoma or chronic lymphocytic leukemia. It would be very encouraging to see CAR T cells play a role in long-term remission, says Ghosh. Physicians do not have long-term data yet, but finding that patients who are refractory to all chemotherapy regimens had remission for at least 1 year would mark tremendous progress in the field.

Ghosh says that the relationship between CAR T-cell therapy and transplant might change if CAR T-cell therapy is moved to an earlier line of treatment, even for chemo-sensitive disease. Physicians do not yet know if CAR T-cell therapy is superior to transplant and whether transplant is necessary for all eligible patients with large cell lymphoma. These are all questions that clinical trials are being designed to answer, states Ghosh.

Dr. Ghosh on the Future of CAR T-Cell Therapy in Patients With Hematologic Malignancies

Nilanjan Ghosh, MD, PhD, physician, Levine Cancer Institute, discusses PET-adapted therapy in patients with Hodgkin lymphoma.

PET-adapted therapy has been referenced for the past 5 to 7 years in Hodgkin lymphoma. It has been used in multiple clinical trials. The reason, states Ghosh, is that more than a decade ago a paper was published that showed that patients with a positive PET scan after 2 cycles of ABVD had poor outcomes. Patients who had a negative PET scan had much better outcomes, states Ghosh.

Many clinical trials were designed to look at ways to improve the outcomes of patients with positive PET outcomes. These patients were dose escalated. One trial used the regimen IGEV followed by autologous transplant. In these trials, patients with positive PET outcomes had a progression-free survival (PFS) in the 60% to 70% range, whereas patients with negative PET outcomes had a PFS in the 80% to 85% range, states Ghosh.

Nilanjan Ghosh, MD, PhD

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