Nilanjan Ghosh, MD

Nilanjan Ghosh, MD, PhD, chief of lymphomas at Atrium Health Levine Cancer Institute, discusses when a Bruton’s tyrosine kinase (BTK) inhibitor would be preferred over a BCL-2 inhibitor as first-line therapy for patients with chronic lymphocytic leukemia (CLL).

The BCL-2 inhibitor venetoclax (Venclexta) plus the anti-CD20 agent obinutuzumab (Gazyva) is a recommended first-line option for patients with CLL, as are the BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence) plus obinutuzumab. According to Ghosh, a BTK inhibitor is preferred over venetoclax in patients with a deletion 17p or 

 mutation due to lower risk of relapse. Venetoclax is administered for a fixed duration of 24 months, while BTK inhibitors can be given indefinitely.

Another concern Ghosh considers for patients receiving venetoclax is the risk of tumor lysis syndrome (TLS), which is mitigated by a 5-week step-up dosing. Older patients, those with renal dysfunction, or those with bulky disease may be at greater risk from TLS. Managing TLS risk may also be difficult for patients who live far from the treatment center.

A head-to-head trial (NCT02477696) showed that acalabrutinib was associated with less cardiotoxicity than ibrutinib, including a 9.4% rate of atrial fibrillation versus 16% with ibrutinib, and fewer discontinuations due to adverse events. Ghosh says this would be a reason to choose acalabrutinib for patients with cardiac comorbidities.

 So if I'm if I'm thinking of using a BTK inhibitor—acalabrutinib or ibrutinib—over venetoclax and obinutuzumab, that's mainly in [patients with] deletion 17p, or patients with a 

 mutation, where I may be a little more worried about defined-time duration therapy, and more comfortable using indefinite BTK inhibition.

Also, in patients who have renal dysfunction, they may have problems with the step-up dosing with the venetoclax even though we do the step-up dosing, tumor lysis risk, and problems in patients who have significantly impaired renal function or advanced age, and also for patients who live far from the center, and perhaps who have very bulky disease, that would be very bulky disease would also put them at high risk of TLS with venetoclax, it's still doable, for sure, but it's just a little bit harder. And so, in those patients, I typically prefer using a BTK inhibitor.

And then, in terms of acalabrutinib over ibrutinib, perhaps patients with cardiac comorbidities; there was a head-to-head study showing lower risk of atrial fibrillation with acalabrutinib over ibrutinib. So, if I'm thinking of somebody who has cardiac comorbidities, [acalabrutinib] comes more in terms of a favorable profile in those patients.

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Nilanjan Ghosh, MD, PhD, discusses when a Bruton’s tyrosine kinase inhibitor would be preferred over a BCL-2 inhibitor as first-line therapy for patients with chronic lymphocytic leukemia. 

Choosing BTK Inhibitors Versus Venetoclax as First-Line CLL Therapy

Nilanjan Ghosh, MD, a hematologist and medical oncologist at the Levine Cancer Institute, Atrium Health, discusses the effect coronavirus disease 2019 (COVID-19) had on using chimeric antigen receptor (CAR) T-cell therapy to treat patients with diffuse large B-cell lymphoma (DLBCL).

Ghosh says that when the pandemic first started, he and other physicians thought it would not only affect CAR T-cell therapy but also stem cell transplants. CAR T-cell treatments for DLBCL include therapies such as axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah). There was a lot of uncertainty around how long the pandemic would last since it started abruptly with many acute cases, which filled intensive care units and hospital beds.

As the months went on, physicians adapted to treating patients during COVID-19, which Ghosh calls the “new normal.” As of October, the pandemic was not affecting the delivery of CAR T-cell therapy for clinical trials and treatment with standard of care in practices. At the beginning of COVID-19, he and his colleagues were doing their best to deliver standard-of-care CAR T therapy, but it did affect CAR T-cell delivery for clinical trials because of regulatory constraints. There were several months where accrual for these trials was limited, but over the past months, many of those constraints have been lifted and the clinical trials have opened back up.

Nilanjan Ghosh, MD, discusses the effect coronavirus disease 2019 had on using chimeric antigen receptor T-cell therapy to treat patients with diffuse large B-cell lymphoma.

Providing CAR T-Cell Therapy for Patients With DLBCL During COVID-19

Nilanjan Ghosh, MD, a hematologist and medical oncologist at the Levine Cancer Institute, Atrium Health, discusses the current unmet needs in mantle cell lymphoma (MCL) and how Bruton’s tyrosine kinase (BTK) inhibitors are being looked at to fill that need for patients with high-risk disease in the first line.

In patients with MCL, BTK inhibitors are used for relapsed/refractory disease. Ghosh says that the results are better if BTK inhibitors are used at treatment earlier in the disease course versus later. Patients with high-risk disease, such as those who have a 

 mutation, deletion, or those who have blastoid morphology, typically do poorly with standard treatments compared to patients with low-risk disease.

If you move BTK inhibitors to the frontline space, how does that compare with standard treatments in this patient population? Ghosh thinks this is an important question in the MCL setting. Trials are ongoing looking at that question for these patients. The PCYC 1143 trial (NCT03112174) is looking at ibrutinib (Imbruvica), a BTK inhibitor, and venetoclax (Venclexta) for high-risk patients, like those with 

 or older patients in the frontline setting. These are unmet needs in this disease landscape.

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Nilanjan Ghosh, MD, discusses the current unmet needs in mantle cell lymphoma and how Bruton’s tyrosine kinase inhibitors are being looked at to fill that need for patients with high-risk disease in the first line.

Exploring Unmet Needs and BTK Inhibitors in the MCL Population

Nilanjan Ghosh, MD, a hematologist and medical oncologist at the Levine Cancer Institute, Atrium Health, discusses the significance of the data from a pilot study of chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel) as treatment of patients who are ineligible for second-line transplant with relapsed/refractory aggressive large B-cell non-Hodgkin lymphoma.

Ghosh says these findings are significant for this older patient population, which has been associated with a poorer prognosis. These patients tend to have highly refractory disease and are older, where the median age is 72 years and 85% of patients are 65 years or older.

The complete response rate in this pilot study was 56%, but long-term data are not yet available, says Ghosh. However, in this population of older, frail patients who tend to have organ dysfunction and other comorbidities, achieving a complete response is more meaningful than a partial response.

Thus far, the responses appear durable, and Ghosh says there may be rationale for moving this treatment to earlier lines. For patients who otherwise do not have any potentially long-term treatment or disease control options, this treatment is a promising option for the field. If the study continued to show similar results as it comes to completion, Ghosh concludes we will be on track to incorporate CAR T-cell therapy into this patient population.

Nilanjan Ghosh, MD, discusses the significance of the data from a pilot study of  lisocabtagene maraleucel in patients ineligible for second-line transplant with relapsed/refractory aggressive large B-cell non-Hodgkin lymphoma.

Nilanjan Ghosh, MD | Authors

Articles

Choosing BTK Inhibitors Versus Venetoclax as First-Line CLL Therapy

Providing CAR T-Cell Therapy for Patients With DLBCL During COVID-19

Exploring Unmet Needs and BTK Inhibitors in the MCL Population

Exploring Updated Data for Large B-Cell Non-Hodgkin Lymphoma