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Mehta-Shah is an associate professor in the Division of Oncology at Washington University School of Medicine in Saint Louis, Missouri.

Dr. Neha Mehta-Shah discusses ways patients with rare blood cancers, such as lymphoma, can better understand their specific subtype of disease.

Breaking Down the Stigma and How to Better Understand Rare Blood Cancers

Among patients with advanced castration-sensitive prostate cancer, health-related quality of life was not statistically different between those receiving Erleada (apalutamide) alone or in combination with Zytiga (abiraterone acetate) and prednisone compared with those receiving androgen-deprivation therapy (ADT) plus Zytiga and prednisone, according to findings in 

Health-related quality of life was evaluated using the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaire and its subscales. The questionnaire was completed at baseline and every four weeks until week 25. FACT-P scores range from 0 to 156, with higher scores indicating better quality of life, according to study authors.

There were no significant differences in baseline mean FACT-P total scores or subscales across the three treatment groups: ADT plus Zytiga and prednisone, 118.5; Erleada, 116.1; and Zytiga and prednisone plus Erleada, 114.9.

Health-related quality of life was maintained during the treatment period, with no statistically significant differences at 25 weeks in mean FACT-P total scores or subscales: ADT plus Zytiga and prednisone, 122.3; Erleada monotherapy, 119.5; and Zytiga and prednisone plus Erleada, 119.9.

The Erleada monotherapy and Zytiga and prednisone plus Erleada groups did not experience meaningful improvements in health-related quality of life compared with the ADT plus Zytiga and prednisone group, except in time to deterioration of the emotional well-being score. This outcome was more favorable in those who received Erleada alone, with a 63% reduction in risk compared with the ADT plus Zytiga and prednisone group, which had a 44% reduction in risk.

A prostate-specific antigen level of 0.2 nanograms per milliliter or lower at week 25 was observed in 31 of 41 patients (75.6%) in the ADT plus Zytiga and prednisone group, 24 of 40 patients (60%) in the Erleada monotherapy group and 31 of 39 patients (79.5%) in the Erleada plus Zytiga and prednisone group. The two-year overall survival rates were 92.5% for the ADT plus Zytiga and prednisone group, 87.9% for the Erleada monotherapy group and 92.7% for the Erleada plus Zytiga and prednisone arm.

Treatment-related side effects of any grade were reported in 30 of 42 patients (71.4%) in the ADT plus Zytiga and prednisone group, 34 of 42 patients (81%) in the Erleada monotherapy group and 36 of 44 patients (81.8%) in the Erleada plus Zytiga and prednisone group.

Grade 3 (severe) and 4 (life-threatening) treatment-related side effects occurred in eight of 42 patients (19%) in the ADT plus Zytiga and prednisone group, seven of 42 patients (16.7%) in the Erleada monotherapy group and 10 of 44 patients (22.7%) in the Erleada plus Zytiga and prednisone group. Lower rates of hot flashes and hypertension were reported in patients who received Erleada monotherapy.

Gynecomastia affected 23 of 42 patients (54.8%), and breast pain was reported by six of 42 patients (14.3%) in the Erleada monotherapy group, both higher than rates observed in the other two groups. No new safety signals were detected in
the study.

“Androgen Receptor Pathway Inhibitor Therapy for Advanced Prostate Cancer: Secondary Analysis of a Randomized Clinical Trial” by Dr. Diogo Assed Bastos et al., 

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In patients with advanced castration-sensitive prostate cancer, health-related quality of life (HRQOL) was similar across treatment groups receiving Erleada (apalutamide) alone, APA plus Zytiga (abiraterone acetate) and Deltasone (prednisone), or ADT plus AAP. The study, published in JAMA Network Open, found no significant differences in HRQOL scores at 25 weeks. However, the APA-alone group showed a more favorable time to deterioration in emotional well-being. PSA levels and overall survival rates were comparable, with varying side effect profiles across treatment groups.

A study found no significant HRQOL differences between Erleada-based therapies and ADT plus AAP for advanced castration-sensitive prostate cancer.

Tumor

Erleada Combo Shows Comparable Quality of Life Outcomes in Prostate Cancer

In a real-world setting, standard-of-care Carvykti (ciltacabta-gene autoleucel) has been shown to elicit responses from nearly all participating patients with relapsed/ refractory multiple myeloma (R/R MM).

Carvykti is a type of chimeric antigen receptor-T (CAR-T ) cell therapy, which, as explained by the National Cancer Institute, involves a patient’s T cells — part
of the immune system — being extracted, changed in a laboratory to attack cancer cells, grown in the laboratory and infused back into the patient.

Overall and complete response rates were 89% and 70%, respectively, in
all patients who received Carvykti, 94% and 74% in 191 patients who received conforming Carvykti and 95% and 76% in 152 patients treated with conforming Carvykti with fludarabine/ cyclophosphamide lymphodepletion.

A comforming treatment is administered according to the specifications of
the FDA’s approval, and lymphodepletion is a short course of chemotherapy administered before CAR-T cell therapy.

 for adults with R/R MM who had received at least four prior lines of treatment. In 2024, the agency approved Carvykti for patients who received at least one prior line of therapy.

, that led to the FDA’s 2022 approval of Carvykti, the overall response rate was 98%, with 83% stringent complete response, according to findings published in 2023.

Patients with R/R MM who underwent leukapheresis, or the collection of healthy white blood cells from a patient, for Carvykti manufacturing at 16 American academic medical centers were included in the study, published in Blood, with 255 patients undergoing leukapheresis and 236 receiving Carvykti.

Of the real-world patients, 54% would not have met the eligibility criteria for CARTITUDE-1.

Senior author Dr. Doris K. Hansen of Moffitt Cancer Center’s Department
of Blood and Marrow Transplant and Cellular Immunotherapy, explained in an interview with 

 why such real-world findings are significant.

“Clinical trials are invaluable because they serve as the gold standard for introducing new therapies and advancing science,” Hansen explained.

“However, clinical trials often have strict eligibility criteria. Patients must meet very specific criteria to participate — they need to have good organ function, stable blood counts and no significant comorbidities."

In contrast, Hansen said, the patients seen in day-to-day clinical practice often have a variety of health challenges, with many patients having comorbid conditions like cardiac issues or renal impairment, and with about 20% of those diagnosed with myeloma experiencing kidney problems. “Additionally,” Hansen said, “some patients may have plasma cell leukemia, amyloidosis or myeloma-related bone damage, which can lead to fractures, pain and even reduced mobility or wheelchair use. These factors often make patients ineligible for clinical trials. ... It is, therefore, very important to report on the experiences of these patients. By studying their outcomes, we can understand how treatments perform in real-world scenarios, as opposed to the controlled, ideal conditions of clinical trials.”

The eligibility criteria for CARTITUDE-1 included adequate organ function, limited comorbidities and having no prior exposure to B-cell maturation antigentargeted therapy.

Cytokine release syndrome was experienced by 75% of patients, with grade 3 (severe) or higher in 5%. Immune effector cell-associated neurotoxicity syndrome was seen in 14%, with grade 3 or higher in 4%. Delayed neurotoxicity was reported in 10% of patients.

Researchers reported a 10% nonrelapse mortality rate, mostly from infections, and noted that second primary malignancies, excluding nonmelanoma skin cancers, were seen in 5.5% of patients and myeloid malignancies/acute leukemia in 1.7%.

 such as Carvykti, as explained by the National Cancer Institute, involves a patient’s T cells, part of the immune system, being extracted, changed in a laboratory to attack cancer cells, grown in the laboratory and infused back into the patient. Carvykti is currently approved by the FDA to be administered in the second line of treatment.

Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma” by Dr. Surbhi Sidana, et al., 

Carvykti (ciltacabtagene autoleucel) demonstrates significant efficacy in real-world settings for relapsed or refractory multiple myeloma, with 89% of patients responding and 70% achieving complete response. Despite many patients not meeting clinical trial criteria, outcomes were comparable to the CARTITUDE-1 trial. At 13 months, median progression-free survival and overall survival were not reached, with 12-month estimates at 68% and 82%, respectively. Side effects included cytokine release syndrome and neurotoxicity. Carvykti, a CAR-T cell therapy, is FDA-approved for patients with multiple prior treatments.

The CAR-T cell therapy Carvykti has been shown to be effective among patients outside the confines of a clinical trial.

Carvykti Effective in Real-World Setting for Myeloma 

Among patients with stage 3 unresectable non-small cell lung cancer (NSCLC), the first participant has been dosed in the phase 2 CONVERGE study, according to a news release from biotechnology company Nanobiotix. The randomized, controlled clinical trial is evaluating the potential first-in-class radioenhancer JNJ-1900 (NBTXR3) in patients being treated with standard-of-care chemoradiation followed by consolidation Imfinzi (durvalumab).

“We believe the true value of [NBTXR3] is driven by its potential to address the unmet needs of the millions of patients each year who receive radiotherapy as part of their treatment,” said Laurent Levy, Chief Executive Officer and Chairman of the Executive Board at Nanobiotix. “With a clear path to potential registration in head and neck cancer established through NANORAY-312, the first patient dosed in the CONVERGE study in [non-small cell lung cancer] NSCLC brings us another step closer to delivering for the large number of patients [NBTXR3] is designed to serve.”

Who is Eligible For CONVERGE Study Enrollment?

According to the clinical trial page
at clinicaltrials.gov, CONVERGE is evaluating the addition of NBTXR3 to concurrent platinum-based doublet chemotherapy with radiation therapy, followed by consolidation immunotherapy, and whether this enhances the objective response rate in patients with locally advanced, unresectable stage 3 NSCLC.

To be considered eligible for enrollment, patients must be candidates for chemotherapy with radiation therapy; have a pathologically confirmed NSCLC diagnosis within three months prior to enrollment; present with unresectable stage 3IIIA or 3IIIB NSCLC; have at least one target lesion suitable for intratumoral or /intranodal injection and external beam radiation therapy; and have an ECOG performance status of 0 or 1.

Participants are considered ineligible for enrollment in the study if they have a history of primary immunodeficiency; organ transplantation requiring immunosuppression; significant cardiac events within three months before enrollment; concurrent or recent malignancies other than NSCLC; and known hypersensitivity to study drugs or components.

Patients with active bleeding diathesis or patients requiring anticoagulation or antiplatelet therapy that cannot be safely modified for procedures are also excluded.

The novel, potentially first-in-class oncology product NBTXR3 comprises functionalized hafnium oxide crystal nanoparticles administered via one-time intratumoral injection and activated by radiotherapy. The proof-of-concept for NBTXR3 was demonstrated in soft tissue sarcomas, leading to the agent receiving a European CE mark in 2019.

The agent’s mechanism of action is designed to induce substantial tumor cell death within the injected tumor when activated by radiotherapy, thereby triggering an adaptive immune response and establishing long-term anticancer memory. Consequently, the company anticipates that NBTXR3 could be applied to any solid tumor treatable with radiotherapy and be adaptable to any therapeutic combination, especially with immune checkpoint inhibitors.

The radiotherapy-activated NBTXR3 is under evaluation for multiple solid tumor indications as a stand-alone treatment and in combination with anti-PD-1 immune checkpoint inhibitors. These initiatives include the global, randomized NANORAY-312 trial, which is focused on locally advanced head and neck squamous cell carcinomas. In February 2020, the Food and Drug Administration granted fast track designation to NBTXR3 activated by radiotherapy, with or without Erbitux (cetuximab), for patients with locally advanced head and neck squamous cell carcinoma who are ineligible for platinum-based chemotherapy.

In 2019, the company entered a comprehensive clinical research partnership with The University of Texas MD Anderson Cancer Center to sponsor multiple phase 1 and 2 trials evaluating NBTXR3 across various tumor types and therapeutic combinations. Nanobiotix announced a license agreement with Janssen Pharmaceuticals, a Johnson & Johnson company, for the global co-development and commercialization of NBTXR3 in 2023.

The phase 2 CONVERGE study has commenced dosing its first participant to evaluate the radioenhancer JNJ-1900 (NBTXR3) in stage III unresectable non-small cell lung cancer (NSCLC) patients. This trial investigates the efficacy of NBTXR3 combined with standard chemoradiation and consolidation durvalumab. NBTXR3, a hafnium oxide nanoparticle, is activated by radiotherapy to induce tumor cell death and an adaptive immune response. The study aims to enhance objective response rates in NSCLC, with eligibility criteria including specific NSCLC stages and performance status, while excluding certain medical conditions.

The first participant has been dosed on the phase 2 CONVERGE study evaluating NBTXR3 in stage III, unresectable non–small cell lung cancer.

Breaking Down the CONVERGE Study of NBTXR3 in Stage 3 Unresectable NSCLC

The woman who raised me and I did not always see eye to eye. In fact, as two stubborn, opinionated characters we frequently bickered, challenged and exchanged choice words with one another. 

As I reflect on 25 years strong with Mom, here are some of my favorite words that we exchanged. We gave each other many cards over the past few years, one of which she had told me she looked for a long time searching for the right message to express her feelings. It reads:

"When you have a daughter who makes you proud, makes you laugh and, very often, makes your day ... you know what joy is. When you have a daughter who is a good person with a gracious heart and generous spirit ... you know what peace is. When you have a daughter whose beauty (inside and out) is matched only by her compassion for others ... you know what love is. Because I have you for my daughter, I know what it is to be truly blessed."

When I first read those words — as I read them now — I feel so close to my mom. Recently, I found a card with the words that expressed how I feel about her. I read this aloud to her on Christmas Day.

"Dear Mom, I'm so grateful for the way I was raised. You were never afraid to be my mother — to put your foot down, to teach me right from wrong, to make sure I did my best. You always let me know I had a mama who cared about me, who believed in me, who was there for me no matter what. Growing up with that kind of love and support made such a difference in my life; it made me who I am today."

My mother was never afraid to voice her opinion or be one to mince words, to put it lightly; but she was always pure in her intentions and true in her actions, and I feel so clearly, so humbly loved. As I go forward, I remember her strength and purity, her fierce sense of pride, her generous heart and sensitivity, her sense of humor (she once packed me a peanut-butter-jelly-and-ham sandwich because I refused to pick one of the two). 

Throughout her life and especially in her fight against lung cancer, Mom set us an example in unconditional devotion, taught our family valuable life lessons and never lost her indomitable spirit.

I know Mom is with us now and always. Goodbyes are only for those who love with their eyes, because for those who love with heart and soul there is no such thing as separation. I love you Mom, Happy New Year. Rest in peace and God bless.

For more news on cancer updates, research and education, don’t forget to

The narrative reflects on a complex yet deeply loving relationship between a daughter and her mother, characterized by mutual respect and understanding despite frequent disagreements. The daughter cherishes the heartfelt words exchanged through cards, highlighting the mother's pride, love, and unwavering support. The mother, who battled lung cancer, exemplified strength, devotion, and humor, leaving a lasting impact on her family. The daughter expresses gratitude for her upbringing and acknowledges the enduring connection with her mother, emphasizing that true love transcends physical separation.

A Tribute to Mom

The management of Waldenström macroglobulinemia (WM), a rare form of blood cancer, requires a nuanced approach with up-to-date treatments and the collaborative treatment of caregivers, according to Dr. Shirley D’Sa.

Utilizing these up-to-date approaches remain vital, as previous therapeutics in this treatment landscape relied heavily on toxic chemotherapies; however, these newer approaches, including BTK inhibitors, have greatly improved outcomes and reduced complications.

D'Sa, a consultant hematologist and clinical lead for the University College London (UCL) Hospital Centre for Waldenström’s Macroglobulinemia and Associated Disorders, sat down for an interview with CURE to delve into the nuances of treating WM.

She also serves as well as an honorary associate professor at the UCL Cancer Institute. She also serves as the hematological lead in the joint neurohematology service at the National Hospital for Neurology, Queen Square, London.

CURE: How has your approach to managing WM, a rare disease, evolved over time?

: I've been involved in the world of WM for about 20 years. I trained and specialized in a hospital in London where I actually started off as a myeloma doctor, and there are many connections between WM and myeloma. The cell types share some characteristics, and in particular, there's the production of proteins which are so key to most people with WM in some form.

So, I began in the myeloma setting, and then I realized that there were a number of WM patients who would be in our clinic, separate from the lymphoma team's clinic. I gradually started putting them to one side and focusing a little bit on them. From a once-every-two-month clinic, it became once a month, then every other week, and now we're seeing 40 patients a week in our WM clinic at our center.

I have to say, during that time, there's been a steady array of advancements in the area and field, which are extremely positive in terms of unified criteria for diagnosis, for response to treatment, and then a range of genetic discoveries that have been made. These discoveries tell us much more about the biology of the disease and how it behaves, how to confirm or refute the diagnosis, and how to differentiate it from other quite similar conditions when you look under the microscope and overall.

How have treatment strategies for WM evolved over the course of your career

Over the years, it's been great; it's been great to witness the developments because, in the beginning, there was just a handful of chemotherapy treatments which, while quite effective in themselves, were also very toxic. The addition of Rituxan (rituximab), an antibody against CD20 found on B cells, which form part of WM, was a help and contributed to the improvement in outcomes. As time went on, in my own practice, we moved a little bit away from medicines like fludarabine. We actually did a number of high-dose chemotherapy treatments in some younger patients, like autologous stem cell transplants, and we tried to focus that treatment on those who were younger and had high-risk WM based on its biological behavior.

One has to bear in mind that back then, there were no targeted therapies for WM, so we had to make the most of chemoimmunotherapy. Regarding immunotherapy or Rituxan, that brings its own challenges, and over the years, we learned through investigators across the globe, notably the Boston group under Stephen Treon, about phenomena such as the Rituxan flare that occurs if IgM is raised and you give Rituxan, potentially causing a quite acute flare, which can lead to hyperviscosity.

So, over the years, we've nuanced the approach to managing WM by using different treatments in a more targeted and careful way, trying to circumvent potential complications. And of course, recently, I would say in the last 10 years, there's been the introduction and advent of targeted therapies, including BTK inhibitors.

At our center, we were involved from the early stages in trials of Imbruvica (ibrutinib) and also Brukinsa (zanubrutinib), both of which have proven to be extremely effective treatments. So yeah, it's been an interesting evolution throughout my career as a specialist because the disease area took off. There was also the gathering of an amazing community of physicians and researchers that continues to this day. And it's such a pleasure to be involved in that group because we work well together, and because WM is a rare disease, it's super important for that to happen. 

Even with all these amazing advancements that have been seen within the world of this disease, 

peripheral neuropathy is a common and debilitating symptom

 of the disease. How do you approach balancing effective treatment with quality-of-life considerations within your practice?

Peripheral neuropathy is common in people with WM, but one has to remember that peripheral neuropathy is also prevalent in the general population. There are hundreds of causes of neuropathy. Some are more common than others, such as diabetes, and frankly, things like excessive alcohol consumption can damage nerves. Anything toxic to nerves over a long period can cause problems. So, we always consider this background when we assess a patient. We don't want to instantly attribute it to WM, because often, it's not the WM causing the problem.

Our approach involves a joint clinic where we see patients together. We bring our respective viewpoints from neurology and hematology. The patient's history is paramount — taking a detailed account of their neuropathy experience. How quickly did it develop? What makes it worse? What makes it better? What is the distribution? Is it mainly in the hands or feet? Do they have other symptoms? Do they have balance problems? Do they have autonomic symptoms, which relate to the autonomic nervous system that regulates blood pressure and appetite? A detailed history is crucial, followed by a clinical examination, particularly of the nervous system.

My colleague conducts this in a very systematic and recorded manner. We then follow up with additional tests, such as imaging scans like MRI and inflammatory nerve antibody testing. The most common antibody is against myelin-associated glycoprotein. Sometimes IgM [immunoglobulin M] antibodies have this property. We sequentially consider the possible causes, and occasionally, we biopsy a nerve if necessary. There's quite a range of possibilities, and only if we feel there is as firm a connection to WM as we can prove — and the patient has progressive symptoms — do we consider offering or recommending treatment.

How do you approach the treatment of this often debilitating side effect?

Ultimately, the treatment involves addressing the underlying WM, because the WM cells are responsible, indirectly via mechanisms like antibody production or occasionally by directly invading nervous tissue. So, it's really about very clear diagnostics, consistent testing, a careful analysis of causality and establishing very good, clear guidelines for each patient.

What are we trying to achieve in that patient? If they have progressive disability, for example, then it's almost an emergency to get them treated. If it's mainly sensory symptoms like pain and loss of temperature, they are less likely to respond well to treatment, and we will then address that with symptomatic measures such as special pain-relieving medication, given in a supervised manner.

Waldenström macroglobulinemia (WM) management has evolved significantly, moving from toxic chemotherapies to targeted therapies like BTK inhibitors, improving patient outcomes. Dr. Shirley D’Sa emphasizes the importance of a collaborative approach in treating WM, particularly in addressing peripheral neuropathy, a common symptom. A detailed patient history and systematic diagnostics are crucial for effective treatment. The integration of neurology and hematology perspectives aids in managing neuropathy, with treatment tailored to individual patient needs. Recent international guidelines provide updated strategies for managing WM-related complications.

An expert reflects on the treatment landscape of Waldenström macroglobulinemia, emphasizing diagnostics, collaboration and managing neuropathy effectively.

Dr. Neha Mehta-Shah

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