James N. Gerson, MD, assistant professor of clinical medicine, Perelman School of Medicine, University of Pennsylvania, discusses clinical trial accrual in mantle cell lymphoma (MCL).

Many patients with MCL will stay in the community, and never get an opinion from an academic center, says Gerson; this is unfortunate because it makes it difficult to offer them the option of participating in up-front clinical trials for their induction therapy.

Certainly, not every patient will want to stay at the University of Pennsylvania, and those at academic institutions do not want to take patients away from community doctors, but sometimes it is good to hear another opinion—especially for those with a rare disease like MCL where there is no standard of care.

Regardless, the institution has no problem accruing to their trials and their staff is constantly managing patients and their toxicities, says Gerson. It is a very exciting time in general to be in academia and to be working with staff on these trials and seeing patients have good outcomes, concludes Gerson.

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James N. Gerson, MD, discusses clinical trial accrual in mantle cell lymphoma.

Dr. Gerson on Clinical Trial Accrual in MCL

James N. Gerson, MD, assistant professor of clinical medicine, Perelman School of Medicine, University of Pennsylvania, discusses clinical trial accrual in mantle cell lymphoma (MCL).

James N. Gerson, MD, discusses clinical trial accrual in mantle cell lymphoma.

James N. Gerson, MD, assistant professor of clinical medicine, Perelman School of Medicine, University of Pennsylvania, discusses recent updates in relapsed/refractory mantle cell lymphoma (MCL).

The majority of advances in MCL in recent years have mostly been made in the relapsed/refractory setting, says Gerson. 

In November 2013, ibrutinib (Imbruvica) was approved by the FDA for use in patients with MCL who received at least 1 prior line of therapy. More recently, in October 2017, acalabrutinib (Calquence) received regulatory approval for the same indication, based on findings from the phase II ACE-LY-004 trial.

Currently, venetoclax (Venclexta) is also under investigation in this space, says Gerson, and the hope is that this agent will demonstrate similar efficacy as has been seen in patients with chronic lymphocytic leukemia.

Going forward, these agents will be examined in novel combinations within the relapsed/refractory space as well as in the up-front setting to improve patient outcomes, concludes Gerson.

James N. Gerson, MD, discusses recent updates in relapsed/refractory mantle cell lymphoma.
 

Dr. Gerson on Updates in Relapsed/Refractory MCL

James N. Gerson, MD, assistant professor of clinical medicine, Perelman School of Medicine, University of Pennsylvania, discusses the emergence of targeted therapy in chronic lymphocytic leukemia (CLL).

Targeted therapy has become the preferred frontline treatment in CLL, explains Gerson. Specifically, ibrutinib (Imbruvica)-based combinations, although venetoclax (Venclexta) and acalabrutinib (Calquence) are also promising agents. Several studies are ongoing to see which agent is the most effective in this patient population and whether these drugs can be used in combination.

Studies presented at the 2018 ASH Annual Meeting showed that, for a majority of patients with CLL, ibrutinib is preferred over chemotherapy with the exception of patients with mutated IGHV, concludes Gerson.

James N. Gerson, MD, discusses the emergence of targeted therapy in chronic lymphocytic leukemia.

Dr. Gerson on Targeted Therapy Versus Chemotherapy in CLL

James N. Gerson, MD, assistant professor of clinical medicine, Perelman School of Medicine, University of Pennsylvania, discusses strategies aimed at alleviating toxicity in older patients with mantle cell lymphoma (MCL).

Most elderly patients with MCL are not candidates for transplant, says Gerson. Rather, these patients are often treated with bendamustine-based therapies, typically bendamustine and rituximab (Rituxan; BR). Recently, the phase III LYM-3002 trial comparing VR-CAP (bortezomib [Velcade], rituximab, cyclophosphamide, doxorubicin, and prednisone) with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone) demonstrated a significant improvement in the VR-CAP arm in transplant-ineligible patients. At a median follow-up of 82 months, median overall survival was 90.7 months in the VR-CAP arm versus 55.7 months in the R-CHOP arm (HR, 0.66; 95% CI, 0.51-0.85; 

 =.001). Accordingly, Gerson commonly uses VR-CAP in transplant-ineligible patients; however, BR can be used as an alternative for older patients who cannot tolerate an anthracycline.

In elderly patients who have a limited volume of asymptomatic disease, rituximab monotherapy may also suffice, concludes Gerson.

Dr. Gerson on Strategies Aimed at Alleviating Toxicity in Older Patients With MCL

James N. Gerson, MD, assistant professor of clinical medicine, Perelman School of Medicine, University of Pennsylvania, discusses the watch-and-wait approach for patients with mantle cell lymphoma (MCL). 

The standard of care for patients with newly diagnosed MCL is induction chemotherapy followed by consolidative transplant if patients are eligible, says Gerson.

However, asymptomatic patients with low tumor burden and favorable prognostic markers like low Ki67 and unmutated 

Though, unlike follicular lymphoma where patients have the potential for spontaneous remission, the majority of patients with MCL will eventually need treatment. According to Gerson, emerging evidence suggests that patients with MCL who undergo a period of observation may not need to be treated the same way as patients who begin treatment at diagnosis. These data are pending but may shed light on optimal treatment strategies for patients who delay treatment.

James N. Gerson, MD, discusses the watch-and-wait approach for patients with mantle cell lymphoma. 

Dr. Gerson on the Watch-and-Wait Approach in MCL

James N. Gerson, MD, assistant professor of clinical medicine, Perelman School of Medicine, University of Pennsylvania,  discusses the phase III CLL14 trial evaluating the combination of venetoclax (Venclexta) and obinutuzumab (Gazyva) versus chlorambucil and obinutuzumab as frontline therapy in chronic lymphocytic leukemia (CLL).

Data from the CLL14 trial served as the basis for the FDA approval of venetoclax and obinutuzumab as frontline therapy for patients with CLL. Data demonstrated that 88.2% (95% CI, 83.7-92.6) of patients treated with the venetoclax combination were progression free at 24 months compared with 64.1% (95% CI, 57.4-70.8) of patients treated with the chlorambucil combination. 

Notably, ibrutinib (Imbruvica) monotherapy is also available to patients in the frontline setting. However, ibrutinib is given indefinitely, Gerson says. Although the data with ibrutinib are more mature, the combination of venetoclax and obinutuzumab may be more appealing to patients as it is given as a fixed treatment course of 1 year. 

Gerson highlights that potential life-long treatment with ibrutinib is not feasible for some patients, so having an alternate option is very exciting. 

James N. Gerson, MD, discusses the phase III CLL14 trial evaluating the combination of venetoclax and obinutuzumab versus chlorambucil and obinutuzumab as frontline therapy in chronic lymphocytic leukemia.
 

James N. Gerson, MD

Articles

Dr. Gerson on Clinical Trial Accrual in MCL

Dr. Gerson on Clinical Trial Accrual in MCL

Dr. Gerson on Updates in Relapsed/Refractory MCL

Dr. Gerson on Targeted Therapy Versus Chemotherapy in CLL

Dr. Gerson on Strategies Aimed at Alleviating Toxicity in Older Patients With MCL

Dr. Gerson on the Watch-and-Wait Approach in MCL

Dr. Gerson on Venetoclax/Obinutuzumab Combination in CLL