Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, interim chief, Section of Hematology/Oncology, director, Lymphoma Program, University of Chicago Medicine, discusses frontline treatment options in mantle cell lymphoma (MCL).

The frontline standard of care for patients with MCL depends on their burden of disease, their age, and their overall fitness, says Smith.

Historically, MCL was thought to be a very aggressive disease, says Smith. However, a subset of patients with nodal disease or leukemic disease have a more indolent presentation and disease course. These patients can be safely observed for a period of time.

Young patients with classic MCL are often considered for aggressive induction therapy followed by autologous stem cell transplant (ASCT) and maintenance rituximab (Rituxan), explains Smith. Conversely, elderly patients or those who are unfit for intensive therapy tend to be given chemoimmunotherapy with maintenance rituximab.

It is not clear whether all patients with MCL should undergo ASCT; however, there is an ongoing trial investigating the role of minimal residual disease after induction therapy. The trial may shed light on the utility of BTK inhibitors in the frontline setting, concludes Smith.

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Sonali M. Smith, MD, discusses frontline treatment options in mantle cell lymphoma.

Dr. Smith on Frontline Treatment Options in MCL


Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, interim chief, Section of Hematology/Oncology, director, Lymphoma Program, University of Chicago Medicine, discusses frontline treatment options in mantle cell lymphoma (MCL).

Historically, MCL was thought to be a very aggressive disease, says Smith. However, a subset of patients with nodal disease or leukemic disease have a more indolent presentation and disease course. These patients can be safely observed for a period of time. 

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, interim chief, Section of Hematology/Oncology, director, Lymphoma Program, University of Chicago Medicine, discusses the different safety profiles of BTK inhibitors in mantle cell lymphoma (MCL).

Three BTK inhibitors have been FDA approved for the treatment of patients with MCL who have received at least 1 prior therapy: ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), says Smith.

Ibrutinib was the first BTK inhibitor to receive regulatory approval, says Smith. The agent had a significant impact on the MCL treatment paradigm after it demonstrated a response rate of approximately 70% with a median duration of response of approximately 1.5 years in this patient population.

However, ibrutinib is also associated with increased off-target toxicities, such as myalgias, atrial fibrillation, increased risk of bleeding, and fatigue, compared with the newer-generation BTK inhibitors.

Acalabrutinib and zanubrutinib may be better tolerated without compromising efficacy for patients; however, the follow up with these agents is much shorter than that of ibrutinib, concludes Smith.

Sonali M. Smith, MD, discusses the different safety profiles of BTK inhibitors in mantle cell lymphoma.

Dr. Smith on Safety Profiles of BTK Inhibitors in MCL

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, discusses the prognosis of patients with indolent non-Hodgkin lymphomas (iNHLs).

Patients with iNHL can be categorized to different subsets of the disease, such as follicular lymphoma, Smith says. For treatment, there are guiding principles physicians can use to help select the appropriate treatment for each patient.

It is important to remember these are chronic malignancies, so patients can live for a very long time. With the long-term expected survival, Smith says it is important to think of both the short-term and long-term side effects of treatment for patients with iNHL. An important principle is that treating patients before they need therapy, however, does not help patients live longer or better, according to the data we have to date, Smith says.

Sonali M. Smith, MD, discusses the prognosis of patients with indolent non-Hodgkin lymphomas.

Dr. Smith on the Guiding Principles for Treating iNHL

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, advises clinicians on diagnosing double-hit and triple-hit lymphoma in patients with diffuse large B-cell lymphoma (DLBCL).

Double-hit and triplet-hit lymphomas are uncommon but not rare, and needs to be looked for in patients diagnosed with DLBCL, Smith says. This subtype is enriched in patients with a germinal center phenotype, as well in those with high-risk features. Smith says that the most important thing is to take a big enough biopsy. If there is a suspicion for an aggressive B-cell lymphoma, Smith advises clinicians to take enough tissue to test for it during initial biopsy.

The most important thing to do when a patient presents with a double-hit lymphoma is to confirm the diagnosis with the pathologist, Smith says. Nuances including amplification, copy number alterations, and mutations can make a difference. Additionally, Smith says that R-CHOP is not going to be sufficient, and clinicians should consider a more intensive therapeutic regimen for these patients.

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, advises clinicians on diagnosing double-hit and triple-hit lymphoma in patients with diffuse large B-cell lymphoma.

Dr. Smith Advises Clinicians on Diagnosing Double-Hit and Triplet-Hit Lymphoma

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, discusses the diagnosis of double-hit lymphoma.

The presence of double-hit lymphoma is relatively uncommon, Smith says, with an incidence of about 5% to 7% in all unselected cases. This is a lot of unselected patients to test by multiple fluorescence in-situ hybridization (FISH) probes to identify a very few number of double-hit cases with a very poor prognosis.

There are different approaches to screening that limit the number of patients who need FISH testing, says Smith. Double-hit lymphoma primarily occurs in patients who have germinal center diffuse large B-cell lymphoma, so some have suggested using the cell-of-origin model to decide which patients need further FISH testing. Another approach is identifying a dual expression of MYC and BCL-2. Smith says that currently, there is no information on which of those will be most cost effective or rational.

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, discusses the diagnosis of double-hit lymphoma.
 

Dr. Smith Discusses the Diagnosis of Double-Hit Lymphoma

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, discusses double-hit and triple-hit lymphoma.

The classification for lymphoma has changed and evolved over the years, Smith says. Certain lymphomas have very aggressive morphologic features, as well as biologic features, that can change the prognosis of a patient if identified. The discovery of these features signaled the need for a change in the classification of lymphoma, Smith says.

The MYC rearrangement, which is classically seen in Burkitt lymphoma, is now known to occur in 10% to 15% of patients with unselected diffuse large B-cell lymphoma. The WHO created a new category after it was discovered that these patients have a poor outcome after R-CHOP therapy. This category is called double-hit or triple-hit high-grade B-cell lymphoma based on the presence of an aggressive B-cell morphology plus a MYC rearrangement, and a BCL2 or BCL6 rearrangement.

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, discusses double-hit and triple-hit lymphoma.
 

Dr. Smith Discusses Double-Hit and Triple-Hit Lymphoma

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, discusses brentuximab vedotin (Adcetris) in cutaneous T-cell lymphoma (CTCL).

In November 2017, the FDA approved brentuximab vedotin as a treatment for patients with CTCL who have received prior systemic therapy. Data from the phase III ALCANZA trial was considered in this approval. Data showed that brentuximab vedotin induced responses lasting at least 4 months in 56.3% of patients versus 12.5% in patients receiving physician’s choice of standard therapies (

 <.001). The data are very exciting, Smith says, and the drug is very well tolerated.

Smith says that this would be her first choice for any patients with CD30 positivity based on its targeted delivery, efficacy, and safety profile. Whether brentuximab vedotin is moved to the frontline setting is challenging. Smith says that this ADC should be tested in patients at the time of transformation. This is a very rare population, most of the studies are very small, and there are no randomized trials in the frontline setting, Smith explains.

Sonali M. Smith, MD, Elwood V. Jensen Professor in Medicine, director, Lymphoma Program, University of Chicago Medicine, discusses brentuximab vedotin (Adcetris) in cutaneous T-cell lymphoma. 
 

Sonali M. Smith, MD

Articles

Dr. Smith on Frontline Treatment Options in MCL

Dr. Smith on Frontline Treatment Options in MCL

Dr. Smith on Safety Profiles of BTK Inhibitors in MCL

Dr. Smith on the Guiding Principles for Treating iNHL

Dr. Smith Advises Clinicians on Diagnosing Double-Hit and Triplet-Hit Lymphoma

Dr. Smith Discusses the Diagnosis of Double-Hit Lymphoma

Dr. Smith Discusses Double-Hit and Triple-Hit Lymphoma

Dr. Smith Discusses Brentuximab Vedotin in CTCL