Zitella Weighs In On Overarching Treatment Strategies in Hematologic Malignancies

Laura J. Zitella, MS, RN, ACNP-BC, AOCN

It is important to keep tolerability top of mind when considering best treatment strategies for patients with hematologic malignancies, according to Laura J. Zitella, MS, RN, ACNP-BC, AOCN.

For example, venetoclax has been available for patients with chronic lymphocytic leukemia (CLL) since 2018, but risk stratification and tumor lysis prevention strategies remain of interest to providers and strategies may differ for those with acute myeloid leukemia or multiple myeloma. Similarly, with the addition of multiple new agents for second- or third-line diffuse large b-cell lymphoma (DLBCL), such as loncastuximab tesirine (Zynlonta), the treatment landscape has become more difficult to navigate.

In an interview with Oncology Nursing News®, Zitella, a hematology/oncology nurse practitioner and associate clinical professor in the Department of Physiological Nursing at the University of California San Francisco, who previously served as the lead advanced practice provider for inpatient hematology/oncology at Stanford Health Care, discusses risk management with venetoclax in patients with CLL, and treatment options for the third-line treatment of patients with DLBCL. Additionally, she discusses the importance of clinical trial enrollment in continuing to advance the treatment landscape for patients.

Zitella recently gave presentations during the 47th Annual Oncology Nursing Society Congress on the practical management of BCL2 inhibitors in CLL and integrating novel therapies into later-line DLBCL care. These presentations centered on correct dosing, risk assessment, and the safety of various drug classes across these different disease types.

Please highlight what optimal dosing with BCL2 inhibitors looks like for patients with CLL.

For patients with CLL, we use a BCL2 inhibitor, and the BCL2 inhibitor that is approved for CLL is venetoclax [Venclexta]. Venetoclax is generally used in combination with an anti-CD20 monoclonal antibody, either obinutuzumab [Gazyva] or rituximab [Rituxan].

One of the adverse effects that we need to be aware of is the risk of tumor lysis. There are a number of different strategies that [may be] implemented in order to prevent tumor lysis syndrome. One of the first things that you do when you are considering using treatment with venetoclax is assess the risk of tumor lysis syndrome. You can classify the risk as low, medium, or high risk. Based on that risk, there are specific guidelines, which are nicely outlined in the package insert, about how much hydration patients need. In addition to hydration, every patient is going to receive allopurinol–unless of course there’s a contraindication or [they have an] allergy to allopurinol. Allopurinol [treatment] starts [approximately one] week before therapy, and then continues throughout the [period of] risk of tumor lysis. For patients who are at very high risk of tumor lysis, they need to be admitted [to the hospital] for the first 2 doses of the dose ramp-up.

Dose ramp up is another one of the strategies to prevent tumor lysis. With venetoclax, there is a dose ramp up over a period of 5 weeks. In the first week, the patient will take 20 mg a day for a week; in the second week, [they will take] 50 mg for a week; [in the third week], 100 mg for a week; [in the fourth week], 200 mg for a week and then, [in the fifth week], 400 mg. The optimal dose of venetoclax for patients with CLL is 400 mg.

By using this dose ramp-up approach, tumor lysis prevention—such as hydration—lab monitoring, and the use of allopurinol, for patients who are very high risk, most cases of significant tumor lysis can be prevented. In clinical trials using all these strategies, only [approximately] 1% of patients had evidence of tumor lysis.

Please discuss how third-line agents may play a role in the treatment of DLBCL.

The standard of care for DLBCL for the past 40 years has been R-CHOP [rituximab plus cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone], which achieves a cure for approximately 60% of patients. For patients whose disease is not cured with R-CHOP chemotherapy, the standard of care has been to use salvage chemotherapy followed by autologous transplant. However, we now have CAR T-cell therapy.

CAR T-cell therapy is basically taking out the patient’s own T cells, sending them to the lab and making them into “killer” T cells. After reintroducing them into the patient, those T cells then proliferate and expand in the body and attack the lymphoma cells. CAR T-cell therapy has really been a major advance and now has moved into the second line setting so that we have an option of using CAR T-cell therapy or salvage chemotherapy, plus transplant for patients. With these approaches, we can cure approximately 30% to 40% more patients.

Patients who progress after autologous transplant or CAR T-cell therapy or who are ineligible for these therapies have a poor prognosis. Recent data show that these patients have an overall survival of approximately 6 months. For that reason, we need additional agents to [address] this unmet need for patients in this situation, unfortunately.

There are a number of new agents that are available and that are beneficial for this patient population. One of those is called loncastuximab tesirine. Some of the primary adverse effects are myelosuppression and the possibility of effusions and elevated gamma-glutamyl transferase. Patients generally [require] steroids the day before treatment, the day of treatment, and the day after treatment. It is administered as an IV [intravenous] infusion.

Another option that we have in this in this setting is tafasitamab-cxix [Monjuvi] and lenalidomide [Revlimid]. This combination has also shown benefit for patients in the third line setting. It is generally well tolerated. Some of the major adverse effects that we see are myelosuppression, rash, and infusion reactions.

The third option in this setting is rituximab, bendamustine [Bendeka], and polatuzumab vedotin [Polivy]. This combination uses rituximab and bendamustine, which is a regimen that we commonly use in lymphoma, in combination with a newer monoclonal antibody-drug conjugate called polatuzumab [which] is a monoclonal antibody directed against CD79, and it is linked to a cytotoxic [payload]. This also increases cytotoxicity.

With this combination, again, a [common] adverse effect would be myelosuppression. You can also see some peripheral neuropathy with polatuzumab and with bendamustine, you do see profound lymphocyte dysfunction—so patients need antibiotic prophylaxis against PJP [pneumocystis jiroveci pneumonia] and also antiviral prophylaxis to prevent herpes simplex virus or varicella-zoster virus.

What is the role of clinical trials in increasing treatment options for patients with hematologic malignancies?

Over the last decade, the rapidity of advances has increased dramatically. And it’s been so exciting to see so many novel therapies [become] available to treat patients and really improve outcomes and improve quality of life.

None of those advances would have been possible without clinical trials. I would encourage every nurse out there to be aware of the available clinical trials and to be educated about clinical trials so that if patients have questions, we can serve as a resource to help encourage them to enroll in clinical trials. I think that’s always a really good treatment option for patients and I think it’s important that patients have access to be able to participate in clinical trials.