BRAIN CANCER

HER2 Breast Cancer

BREAST CANCER

Bladder Cancer

Prostate Cancer

Renal Cell Carcinoma

GENITOURINARY CANCERS

Liquid Biopsies

GENOMIC TESTING

Colorectal Cancer

GIST

Gastric Cancer

GI CANCERS

Cervical Cancer

Endometrial Cancer

Ovarian Cancer

GYNECOLOGIC CANCERS

HEAD & NECK CANCERS

Bone Marrow & Stem Cell Transplant

HEMATOLOGY

CAR T-Cell Therapy

IMMUNOTHERAPY

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

LEUKEMIAS

Biomarker-Driven Lung Cancer

EGFR+ Lung Cancer

MET-Targeted Therapy

Small Cell Lung Cancer

LUNG CANCER

DLBCL

Follicular Lymphoma

Mantle Cell Lymphoma

LYMPHOMAS

MPNs

MULTIPLE MYELOMA

NTRK GENE FUSIONS

SARCOMA

Melanoma

SKIN CANCERS

THYROID CANCERS

NEWS

All News

FDA Briefs

Oncology Icons

Special Reports

The Targeted Pulse

Voices from the Field

CONFERENCES

Conference Coverage

Conference Listing

Data Dialogue with the Oncology Brothers

MEDIA

All Videos

Case-Based Peer Perspectives

Expert Perspective Virtual Tumor Board

Interviews

Investigator Perspectives

Medical World News

Pivotal Practice Views with the Oncology Brothers

Podcasts

Precision Medicine

Speaking Out

PUBLICATIONS

All Publications

Evolving Paradigms

Peers & Perspectives in Oncology

Targeted Therapies in Oncology

CASE-BASED ROUNDTABLE

PARTNERS

RESOURCES

CME/CE

Clinical Trials

Precision Medicine Perspectives

Press Releases

Treatment Resources

SUBSCRIBE

Targeted Oncology provides news, videos, and reviews on the rapidly evolving world of targeted therapies and immunotherapy for oncologists treating patients in a community setting.

About Us

Advertise

Contact Us

CureToday.com

CancerNetwork.com

OncLive.com

OncNursingNews.com

Do Not Sell My Information

Privacy

Terms & Conditions

Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways

Facebook

Linkedin

YouTube

Instagram

Featured Clinical Focus

BTK Inhibitors: In-Focus

Bone Marrow & SCT

EGFR-Positive Lung Cancer

Lung Cancer

Multiple Myeloma

Thyroid Cancers

Clinical Focus

Brain Cancer

Breast Cancer

Gastrointestinal Cancer

Genitourinary Cancers

Gynecologic Cancers

Head & Neck Cancers

Hematology

Leukemias

Lymphomas

Sarcoma

Skin Cancers

Spotlight

1rem

Clinical

Andre H. Goy, MD; Sandra M. Swain, MD, FACP, FASCO Associate Dean for Research; Carolina Bernabe Ramirez, MD; Jonathan E. Rosenberg, MD; David H. Vesole, MD, PhD, FACP Director, Myeloma Program; Isabel Preeshagul, DO, MBS  
 

Community Practice Connections™: 5th Annual Precision Medicine Symposium – An Illustrated Tumor Board

Karen M. Winkfield, MD, PhD; Narjust Florez, MD, FASCO; Gilberto de Lima Lopes Junior, MD, MBA, FASCO; Coral Olazagasti, MD; Vonetta M. Williams, MD, PhD

 Fighting Disparities and Saving Lives: An Exploration of Challenges and Solutions in Cancer Care

PHA-22-TTD0589 - /clinical/cll

Current frontline treatment options for patients with chronic lymphocytic leukemia (CLL) have grown over the past year, specifically with the approval of 2 Bruton’s tyrosine kinase (BTK) inhibitors. Notably, in January 2023, 

 (Brukinsa) for adult patients with CLL or small lymphocytic leukemia (SLL) based on data from 2 phase 3 randomized studies: ALPINE (NCT03734016) and SEQUOIA study (NCT03336333).

In the phase 3 ALPINE trial, investigators assessed treatment with zanubrutinib vs ibrutinib (Imbruvica) in patients with relapsed/refractory CLL.

Of the 415 evaluated patients included in the study, the overall response rate (ORR) among those treated with zanubrutinib was 80% (95% CI, 76-85) vs 73% (95% CI, 68-78) in the ibrutinib arm (HR, 1.10; 95% CI, 1.01-1.20; 

 =.0264). After a median follow-up of 14.1 months, the median duration of response (DOR) was not reached in either arm.

In the SEQUOIA trial, zanubrutinib was compared with bendamustine and rituximab (Rituxan) in treatment of treatment-naïve patients with CLL. Here, the median progression-free survival (PFS) was not reached in the zanubrutinib arm vs 33.7 months (95% CI, 28.1-NE) in the bendamustine and rituximab arm (HR, 0.42; 95% CI, 0.28-0.63; 

 ≤ .0001). The estimated median follow-up was 25.0 months.

A total of 110 patients were given zanubrutinib within a separate non-randomized cohort of the study. Of these patients, all had previously untreated CLL/SLL with 17p deletion. In this cohort, the ORR was 88% (95% CI, 81-94), and the median DOR was not reached after a median follow-up of 25.1 months.

The most frequent adverse events seen in at least 30% of patients who received zanubrutinib included neutrophil count decrease (42%), upper respiratory tract infection (39%), platelet count decrease (34%), hemorrhage (30%), and musculoskeletal pain (30%). Zanubrutinib was generally well-tolerated among patients with CLL, low rates of atrial fibrillation were strong efficacy seen compared [with] ibrutinib and chemoimmunotherapy.

Current frontline treatment options for patients with chronic lymphocytic leukemia have grown over the past year, specifically with the approval of zanubrutinib.

Understanding the Role of Zanubrutinib for the Treatment of CLL

In season 4, episode 7 of Targeted Talks, Cyrus M. Khan, MD, a hematologist at Allegheny Health Network, discusses the latest FDA activity in the chronic lymphocytic leukemia (CLL) space.

Beginning with the early 2023 FDA approval of zanubrutinib (Brukinsa) for the treatment of adult patients with CLL and small lymphocytic leukemia (SLL), Khan explains that the Bruton’s tyrosine kinase (BTK) inhibitor demonstrated non-inferiority compared with the standard-of-care (SoC) combination of bendamustine and rituximab (Rituxan). This approval was granted based on findings from the ALPINE (NCT03734016) and SEQUOIA (NCT03336333) studies.

“Both studies showed that the use of zanubrutinib produced superior results for these patients. In the case of the ALPINE study, the 24-month [progression-free survival] rate was 79.5% with the next generation BTK inhibitor compared with 67.3% for patients on ibrutinib [Imbruvica],” said Khan in the interview with Targeted Talks.

Recently, the FDA Oncologic Drugs Advisory Committee (ODAC) also voted against the approval of duvelisib (Copiktra) for the treatment of relapsed or refractory CLL/SLL. Khan highlights the ODAC discussion on duvelisib and other PI3K inhibitors, as well as the findings from the phase 3 DUO trial (NCT02004522), which support the new drug application.

“The problem with these drugs has been the side effect profile. We’ve had autoimmune problems come up, like pneumonitis, transaminitis, colitis, etc., and infectious complications. Then, in some of the studies, the overall survival has been poorer on PI3 kinase inhibitors rather than the standard of care,” says Khan.

During the discussion, Khan also talks about the tablet formulation of acalabrutinib (Calquence) being approved to improve absorption in patients, and agents newly granted fast track and orphan drug designations by the FDA. According to Khan, an agent to watch is the BTK inhibitor pirtobrutinib (Jaypirca), which is under investigation in the phase 1/2 BRUIN study (NCT03740529).

“Patients do progress on BTK inhibitors…I’m hoping that drug gets approved for patients that progress on the current BTK inhibitors,” Khan says.

In season 4, episode 7 of Targeted Talks, Cyrus M. Khan, MD, discusses the latest FDA activity in the chronic lymphocytic leukemia space.

Exciting Activity in Chronic Lymphocytic Leukemia

In season 3, episode 4 of Targeted Talks, Alexey Danilov, MD, PhD, associate director, Toni Stephenson Lymphoma Center, and professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, discusses the shift toward utilizing cellular therapy to treat high-risk patients with chronic lymphocytic leukemia (CLL).

The definition of high-risk has changed in CLL based on the emergence of better therapies. Today, patients with 

 mutations, complex karyotype, and patients who have progressed while on targeted therapies are considered to be high risk.

Historically for the high-risk CLL population, allogeneic stem cell transplant and chemoimmunotherapy were the standards of care. The treatment landscape has since expanded to include Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors. These newer drug classes can be used sequentially and in the clinical trial setting, they are being investigated as combinations. PI3K inhibitors are also available and effective for the treatment of high-risk CLL.

The role of transplant is after patients progress on available targeted therapies.

In terms of cellular therapies have been another positive development for high-risk CLL, says Danilov. In studies, responses to chimeric antigen receptor (CAR) T-cell therapy have been observed in patients with deletion 17p and those who are refractory to BTK inhibitors. The next step with CAR T cells is understanding the durability of response and learning better ways to handle severe toxicities like cytokine release syndrome.

The latest treatment strategies being investigated for high-risk CLL include CAR T-cell therapy combined with targeted therapies, novel BTK inhibitors for BTK-refractory patients, and natural killer cells, explains Danilov.

In season 3, episode 4 of Targeted Talks, Alexey Danilov, MD, PhD, discusses the shift toward utilizing cellular therapy to treat high-risk patients with chronic lymphocytic leukemia.

Better Strategies for the Treatment of High-Risk Chronic Lymphocytic Leukemia

The FDA updated the fludarabine phosphate injection labeling under Project Renewal, clarifying the dosage for combination therapy and streamlining safety warnings.

FDA Updates Fludarabine Labeling Under Project Renewal Initiative

Nicole Lamanna, MD, discussed some of the ongoing clinical trials evaluating new therapies for patients with chronic lymphocytic leukemia.



Exploring New Therapies and Sequencing in Relapsed CLL

Cyrus M. Khan, MD, discussed recent advancements in CLL treatment, particularly the shift to nonchemotherapy options and the availability of CAR T-cell therapy.

Advancements in CLL: CAR T, BTK Inhibitors and Personalized Medicine

Susan L. Slager, PhD, discussed the etiology and inherited genetic factors that are associated with the risk of chronic lymphocytic leukemia.

Genetic Risk Score Offers Insight Into CLL Predisposition

John Seymour, MD, discusses the development and clinical application of BCL-2 inhibitors for the treatment of CLL. 

Breakthroughs and Challenges in BCL-2 Inhibitor Therapy for CLL Treatment

Managing Patients With Chronic Lymphocytic Leukemia

Alessandra Ferrajoli, MD, hematologist/oncologist, associate professor of medicine, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the importance of supportive care in the management of patients with chronic lymphocytic leukemia (CLL) with comorbidities.

Ferrajoli presented on this topic and more during a session that she was a part of at the 2024 Society of Hematologic Oncology (SOHO) Annual Meeting.

In addition, she highlights some of the key strategies that she believes should be integrated when managing and treating patients with CLL.

There are several things that we can do to optimize care [of patients with CLL]. For cardiovascular comorbidity, it is very important to do a cardiac workup and work very closely with cardio oncologists so that they can tell us whether the treatment of the cardiovascular comorbidity is optimized, and so they can also give us their expert opinion on whether those patients are fit to receive certain type of therapies.

Another very important point, in my view, is to make sure that the patients are up to date on their immunizations, because there [are] data that show that once you start treatment, your ability to respond to immunization is lessened. So, it is important that patients receive their pneumonia vaccination, their shingle vaccination, and whenever it is possible, the seasonal ones, such as flu or COVID-19, before they start treatment, so that they optimize whatever is their ability to then respond to those infection and it is the same thing is for cancer screening. It is very important that before we start the treatment for our patients, we make sure they are up to date on their cancer screening so that we do not have to deal with 2 problems at the same time.

Videos

Alessandra Ferrajoli, MD, discusses the importance of supportive care in the management of patients with chronic lymphocytic leukemia with comorbidities.


News

Revolutionizing CLL Care With Targeted and Cellular Therapies

Cyrus M. Khan, MD, hematologist in the Division of Hematology and Cellular Therapy at West Penn Hospital of Allegheny Health Network, highlights some of the most recent and significant advancements in chronic lymphocytic leukemia (CLL) treatment.


In recent years, there have been significant advancements in non-chemotherapy treatments for CLL, including the approval of targeted therapies and immunotherapies. One major breakthrough, according to Khan, is the approval of chimeric antigen receptor (CAR) T-cell therapy for patients with CLL, especially those who have not responded to other treatments.

Bruton’s tyrosine kinase (BTK) inhibitors like ibrutinib (Imbruvica), zanubrutinib (Brukinsa), and acalabrutinib (Calquence) have been effective, but until recently, there were no options for patients who progressed on these drugs. Now, Khan explains that a new BTK inhibitor, pirtobrutinib (Jaypirca), offers an alternative for these patients, representing yet another significant progress in CLL treatment options.

We have had a lot over the last few years, a lot of advancements, [especially] as non-chemotherapeutic interventions are concerned. For example, we have had a lot of targeted agents that have been approved, a lot of immunotherapy. I think the newest advancement has been the approval of CAR T-cell therapy now for patients with CLL, which is the most sort of advancement.

We have also had BTK inhibitors like ibrutinib, zanubrutinib, and acalabrutinib for quite some time, and they’ve been very effective treatments. However, until recently, we didn’t have a solution for patients who progressed on those BTK inhibitors. Now, we have a new drug called pirtobrutinib, which works for patients who have progressed on any of the three BTK inhibitors. This allows patients to continue with an oral treatment option.

Then we never had a great cellular therapy option for patients who had progressed on the standard oral treatments and immunotherapies. Now, fortunately, CAR T-cell therapy is available for those patients as well, and it has been effective. This is a major breakthrough for patients with CLL.

Cyrus M. Khan, MD, highlights some of the most recent and significant advancements in chronic lymphocytic leukemia treatment.


Ferrajoli on the Impact of Comorbidities and Available Therapies in CLL

Alessandra Ferrajoli, MD, hematologist/oncologist, associate professor of medicine, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the comorbidities that can impact the management of patients with chronic lymphocytic leukemia (CLL) and some of the available treatment options in this space, including BCL2 inhibitors and Bruton's tyrosine kinase (BTK) inhibitors.

 So, there are 2 main comorbidities that we look at in this specific situation. One is renal failure, and that is very important for the BCL2 inhibitors because those agents need to be given to patients that have a certain creatinine clearance, at least 35 CC per minute. They have to maintain renal function because of the risk of what we call tumor lysis syndrome. That is a release of chemicals in your bloodstream related to the effect of the therapy on leukemia. For BTK inhibitors, instead, the main toxicity we look at is cardiovascular history, in particular, the risk for arrhythmias, prior history of arrhythmias, or ongoing cardiac arrhythmias.

Since we live at what I call an age of plenty, those treatments are very good. So, we can just start with the one that we feel is the best fit for that patient. For example, if a patient has a compromised renal function or there is a tumor bulk that is such that I will be worried in regard to tumor lysis syndrome, then I will probably steer that patient toward the program that contains mostly BTK inhibitors. If it is a patient that has had a lot of problems with atrial fibrillation, atrial fibrillation that tends to be recurrent, that is difficult to control, or hypertension that is very difficult to control, a history of hypertensive emergencies, then I will say that patient should not receive certain BTK inhibitors, and is best, probably, to use BCL2 inhibitors.

 As far as BCL2 inhibitors, we have venetoclax [Venclexta] that is available, and then we have another agent called sonrotoclax [BGB-11417], and that is in clinical trials. For BTK inhibitors, the list is much longer. We have ibrutinib [Imbruvica], that was the first one that was developed, and it is considered a first-generation BTK inhibitor. Then, we have second-generation BTK inhibitors, and we have 2 that are approved: Acalabrutinib [Calquence] and zanubrutinib [Brukinsa]. Now, we also have a new type of BTK inhibitor. They are the non covalent BTK inhibitor, and we have pirtobrutinib [Jaypirca].

Alessandra Ferrajoli, MD, discusses the comorbidities that can impact the management of patients with chronic lymphocytic leukemia and some of the available treatment options in this space.

Ferrajoli’s Highlights From SOHO 2024 on CLL Therapy

Alessandra Ferrajoli, MD, hematologist/oncologist, associate professor of medicine, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the session she was a part of at the 2024 Society of Hematologic Oncology Annual Meeting.

Here, she highlights some of the key takeaways for oncologists treating patients with chronic lymphocytic leukemia based on the presentation.

 We had the pleasure of reviewing how to manage toxicities with targeted therapy in patients with chronic lymphocytic leukemia, and we went and reviewed how we manage toxicity and the relevant toxicity and components that we look at when we treat patients with BCL2 inhibitors. That was the first presentation by Barbara F. Eichhorst, MD. And then we moved to the [Bruton’s tyrosine kinase (BTK) inhibitors, and that was from Lydia Scarfò, MD. And then, because now things are really moving in the combination field, where we use both targeted therapy, BCL2 targeted and BTK targeted therapy together, we then had Catherine C. Coombs, MD, gave us a review regarding combinations.

 There were some important points that were presented. There was very interesting data that compared all the different [adverse] effects with all the targeted therapy that were presented by Dr. Eichhorst, and showed how maybe some BTK may be a little bit better tolerated than others. Definitely the second-generation seems to have less toxicity than the first-generation. But also, she gave some tips on how to handle patients that present with a very high white [blood cell] count. She presented that experience with bendamustine to reduce the white count, and I think that was particularly important.

Then when we moved to the combos, there was also very nice data showing how most of the combination trials that use both BTK inhibitors and BCL2 inhibitors, and sometimes even with the third element of an anti-CD20 monoclonal antibodies, as long as you monitor for neutropenia, that seems to be the most common toxicity, are actually very well-tolerated too.

Alessandra Ferrajoli, MD, discusses the session she was a part of at the 2024 Society of Hematologic Oncology Annual Meeting. 


Next Steps for Acalabrutinib/Obinutuzumab in Treatment-Naive CLL

Jeff Sharman, MD, medical director of hematology research at US Oncology, discusses the clinical implications for oncologists based on data from the 


The study sought to assess treatment with acalabrutinib (Calquence) with or without obinutuzumab (Gazyva) in treatment-naive chronic lymphocytic leukemia (CLL). Here, Sharman also discusses potential avenues for future research in light of the 6-year follow-up results from the study.

 I think if a patient is going to be treated with a [Bruton’s tyrosine kinase (BTK)] inhibitor, particularly acalabrutinib, I think that the physician needs to have a thoughtful discussion with their patients about whether or not to add the additional anti-CD20 antibody. I do think that a growing number of key opinion leaders have started doing that more frequently. It still remains a little bit controversial, so we will see how this is received by the field. I hope it sparks some conversation.

 There are a handful of approaches you can take to treat a previously treated [patient with] CLL. That could be BTK monotherapy. It could be obinutuzumab with a BTK inhibitor. It could be obinutuzumab with venetoclax [Venclexta] or a BTK [inhibitor] with a BCL2 [inhibitor]. There are really 4 different strategies emerging. We want to know what is going to be the best one. We are currently conducting a randomized study in which all patients receive venetoclax and half receive obinutuzumab, half receive acalabrutinib, and I am hoping that that gives us some good insight into picking optimal first-line therapy, but there are patients where we are not going to want to choose venetoclax. For those patients, acalabrutinib in combination with obinutuzumab represents a good option.

Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib ± obinutuzumab Vs obinutuzumab + chlorambucil in treatment-naive chronic lymphocytic leukemia: 6-year follow-up of Elevate-TN. 

. 2023; 142(Suppl 1): 636. doi:10.1182/blood-2023-174750

Jeff Sharman, MD, discusses the clinical implications for oncologists based on data from the ELEVATE-TN trial.


Evaluating Tumor Lysis Syndrome in CLL/SLL Treated With Venetoclax 

Yannis K. Valtis, MD, second-year fellow in medical oncology at Memorial Sloan Kettering Cancer Center, provides background on a single-institution, retrospective cohort study which assessed laboratory and clinical tumor lysis syndrome in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

The study evaluated patients who were given commercial venetoclax (Venetoclax) in any line of treatment at Memorial Sloan Kettering Cancer Center between January 1, 2016, and December 31, 2020.

https://www.targetedonc.com/view/real-world-findings-on-tls-prevention-and-management-with-venetoclax-in-cll

Yannis K. Valtis, MD, provides background on a single-institution, retrospective cohort study which assessed laboratory and clinical tumor lysis syndrome in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

Chronic Lymphocytic Leukemia

Latest News