R. Gregory Bociek, MD, associate professor of internal medicine, Division of Oncology and Hematology, program director, Hematology/Oncology Fellowship Program, University of Nebraska Medical Center, discusses the clinical uncertainty of minimal residual disease (MRD) negativity in chronic lymphocytic leukemia (CLL).

The phase 2 CAPTIVATE trial demonstrated that the 1-year disease-free survival (DFS) ​rate in patients with CLL or small lymphocytic lymphoma who ​had undetectable MRD and received ibrutinib (Imbruvica) was not significantly different compared with the 1-year DFS rate in patients who received placebo.

Although the data provided proof of principle that MRD could have clinical implications for patients with CLL, the role of MRD negativity in terms of treatment selection for patients with CLL remains largely unknown, says Bociek.

For example, if a patient finishes 6 cycles of bendamustine plus rituximab (Rituxan) or a year of induction therapy with venetoclax (Venclexta) plus obinutuzumab (Gazyva), MRD testing can indicate whether the patient has residual disease but cannot inform whether the patient should remain on venetoclax, says Bociek. As such, prospective data are needed to answer the clinically relevant question of what MRD status means in terms of treatment selection, concludes Bociek. 

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R. Gregory Bociek, MD, discusses the clinical uncertainty of minimal residual disease negativity in chronic lymphocytic leukemia. 



Dr. Bociek on the Clinical Uncertainty of MRD Negativity in CLL 

R. Gregory Bociek, MD, an associate professor of internal medicine, Division of Oncology and Hematology and program director, Hematology/Oncology Fellowship Program, University of Nebraska Medical Center, discusses the role of minimal residual disease in patients with chronic lymphocytic leukemia (CLL).

One trial that examined the role of MRD in CLL was the phase 2 CAPTIVATE trial (NCT02910583), where patients with CLL received 3 cycles of ibrutinib (Imbruvica), followed by 12 cycles of the combination ibrutinib plus venetoclax (Venclexta). After 12 months of treatment with the combination, patients are assessed for MRD; those who are confirmed to have undetectable MRD are then randomized to either continue ibrutinib or placebo, Bociek explains.

To answer the question of whether putting patients with undetectable MRD on more treatment, which comes with added cost and toxicity, is beneficial, Bociek notes. This study will help to clarify whether this patient population needs more therapy after initial induction, Bociek says. Additionally, patients who do have MRD on this trial will be randomized to either single-agent ibrutinib or continuation of the ibrutinib/venetoclax combination. The outcomes observed with these approaches will help guide future therapy decisions, Bociek concludes.

R. Gregory Bociek, MD, discusses the role of minimal residual disease in patients with chronic lymphocytic leukemia. 


Dr. Bociek on the Role of MRD in CLL

R. Gregory Bociek, MD, an associate professor of internal medicine, Division of Oncology and Hematology and program director, Hematology/Oncology Fellowship Program, University of Nebraska Medical Center, discusses the rationale to reserve allogeneic stem cell transplant (allo-SCT) for certain patients with chronic lymphocytic leukemia (CLL). 

Currently, the only patients with CLL who are considered for allo-SCT are those who are young, fit, and have progressed on multiple lines of therapy, such as BTK inhibitors and venetoclax (Venclexta), says Bociek. In these scenarios, patients would have to have a fully matched donor or a sibling donor, Bociek explains. Moreover, moving forward with transplant requires significant discussion with the patient. However, in these rare cases, allo-SCT may be optimal, especially because CAR T-cell therapy is not as developed as it is in diffuse large B-cell lymphoma and mantle cell lymphoma, explains Bociek. 

Despite the risk of transplant-related complications or death, young patients with CLL may not have sufficient treatment options available to derive 2 to 4 years of disease-free survival, Bociek says. Although the majority of patients with CLL are older, younger patients could be considered for allo-SCT, concludes Bociek.

R. Gregory Bociek, MD, discusses the rationale to reserve allogeneic stem cell transplant for certain patients with chronic lymphocytic leukemia.  



Dr. Bociek on Reserving Allo-SCT for Certain Patients with CLL 

R. Gregory Bociek, MD, an associate professor of internal medicine, Division of Oncology and Hematology and program director, Hematology/Oncology Fellowship Program, University of Nebraska Medical Center, discusses outcomes for patients with chronic lymphocytic leukemia (CLL) and COVID-19.

One retrospective, multi-institutional study included 198 patients with COVID-19 and CLL across 43 institutions, according to Bociek. Data showed that approximately one-third of patients will not survive; the overall case fatality rate was 33%, Bociek says. Additionally, one-third of patients were intubated, or admitted to the intensive care unit, and 90% of patients were hospitalized.

Despite the fact that the investigators have done their best to collect data, they're more likely to think of patients who are sicker, according to Bociek. Additionally, the first few papers to be released could make the situation seem more dire than it actually is, Bociek adds. However, several lessons can still be taken away from the paper, such as that patients with more comorbidities and organ dysfunction may represent more challenging cases, Bociek concludes.

R. Gregory Bociek, MD, discusses outcomes for patients with chronic lymphocytic leukemia and COVID-19.

Dr. Bociek on Outcomes of Patients With CLL and COVID-19

R. Gregory Bociek, MD, associate professor of internal medicine, Division of Oncology and Hematology, program director, Hematology/Oncology Fellowship Program, University of Nebraska Medical Center, discusses the evolving role of prognostic factors in chronic lymphocytic leukemia (CLL).

Real-world data have reported that prognostic testing for fluorescence in situ hybridization (FISH) cytogenetics and immunoglobulin heavy chain (IgH) status is underutilized in patients with CLL, which can lead to poorer outcomes in patients with poor-risk genetics who are treated with chemoimmunotherapy. Although most patients with CLL will respond well to ibrutinib (Imbruvica) understanding their mutational status can help inform prognosis, Bociek explains. 

Moreover, if patients do not want to receive ibrutinib or fixed-duration venetoclax (Venclexta) and prefer bendamustine plus rituximab (Rituxan) or fludarabine, cyclophosphamide, and rituximab (FCR), getting prognostic testing is critical, says Bociek. However, testing for FISH cytogenetics or IgH status is becoming less important as more novel targeted therapies are introduced to the CLL paradigm. Moreover, these markers could become less relevant in the coming years as minimal residual disease and other molecular or biologic features take on a greater role for prognostication in CLL, concludes Bociek. 

R. Gregory Bociek, MD, discusses the evolving role of prognostic factors in chronic lymphocytic leukemia.  



Dr. Bociek on the Evolving Role of Prognostic Factors in CLL 

R. Gregory Bociek, MD, associate professor of internal medicine, Division of Oncology and Hematology, program director, Hematology/Oncology Fellowship Program, University of Nebraska Medical Center, discusses the evolving role of chemoimmunotherapy in chronic lymphocytic leukemia (CLL).

Some patients with CLL require immediate therapeutic intervention for symptoms or rapidly progressing disease, whereas others can remain on active surveillance for decades, explains Bociek. Currently, the role of chemoimmunotherapy is diminishing among novel targeted options that confer improved survival vs chemoimmunotherapy. 

However, young, fit patients with favorable genetics and a mutated phenotype could still be considered for chemoimmunotherapy, especially if they are interested in receiving a time-limited option, Bociek explains. A significant proportion of these patients could obtain a durable response for many years with a 6-month course of chemoimmunotherapy.

Additionally, treatment-related and financial toxicities associated with targeted therapies alone or in combination with monoclonal antibodies may prevent some patients from receiving these newer treatments, says Bociek. Moreover, although some newer time-limited targeted options exist, many of these options require continuous dosing, concludes Bociek.

R. Gregory Bociek, MD, discusses the evolving role of chemoimmunotherapy in chronic lymphocytic leukemia.  



R. Gregory Bociek, MD

Articles

Dr. Bociek on the Clinical Uncertainty of MRD Negativity in CLL

Dr. Bociek on the Role of MRD in CLL

Dr. Bociek on Reserving Allo-SCT for Certain Patients with CLL

Dr. Bociek on Outcomes of Patients With CLL and COVID-19

Dr. Bociek on the Evolving Role of Prognostic Factors in CLL

Dr. Bociek on the Evolving Role of Chemoimmunotherapy in CLL