Ryan McDonald

The use of short duration Kyprolis (carfilzomib) combined with the chemotherapy cyclophosphamide and the steroid dexamethasone was associated with comparable results to upfront autologous stem cell transplantation (ASCT) in newly diagnosed, transplant-eligible (NDTE) patients with multiple myeloma, according to recent findings.

Data currently support the use of ASCT in these patients; however, those trials have employed the chemotherapy lenalidomide as maintenance therapy. The concern is that lenalidomide has been shown to mostly benefit patients with standard-risk disease. Moreover, ASCT among this patient population is associated with high minimal residual disease (small number of cancer cells in the body following treatment) rates following initial and short duration treatment strategies.

As a result, the study authors aimed to assess the effect of Kyprolis-based short term and maintenance treatments versus ASCT in this patient population.

Patients at pre-randomization received four cycles of 56 mg/m2 of Kyprolis in a bi-weekly regimen along with 500 mg of cyclophosphamide and 40 mg of dexamethasone weekly. Patients who achieved at least a partial response to therapy proceeded to peripheral blood stem cell harvests (procedure to collect some stem cells from a person’s blood) and were then randomized to receive either the chemotherapy melphalan at 200 mg/m2 plus ASCT or four cycles of the Kyprolis-based regimen. The study population then received 18 cycles of maintenance Kyprolis at 56 mg/m2 weekly.

During the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, the study’s lead author Dr. Kwee Yong, of University College London Hospitals NHS Foundation Trust, presented results that evaluated progression-free survival (time during and after treatment when the patient lives without disease progression).

The trial enrolled 281 patients (median age, 59 years), of which 47.3% were aged older than 60 years. All patients received initial treatment with the Kyprolis-based regimen and were then randomized. At the time of randomization, outcomes were similar between the ASCT (109 patients) and short-duration Kyprolis-based (109 patients) groups.

Two hundred and twenty-eight patients proceeded to stem cell collection, and 197 patients started maintenance therapy. Following initial treatment, VGPR rate was 58.5%, which increased to 77.3% after the short-duration Kyprolis-based regimen and 80% after ASCT. The minimal residual disease-negative rate after initial treatment was 24.3%, which increased to 35.8% after short-duration treatment and 53.1% after ASCT.

Among patients considered to have standard risk disease, VGPR rate after initial treatment with the Kyprolis-based regimen (207 patients) was 58.5%, which increased to 79.5% with the short-duration Kyprolis-based treatment (79 patients) and 76.8% with ASCT (85 patients). The minimal residual disease-negative rate was 25% after initial treatment, 37.1% with short-duration treatment and 48.1% with ASCT. The results, Yong noted, were relatively similar in the high-risk patient population. In those individuals, VGPR rate after initial treatment (52 patients) was 59.6%, 77.3% after short-duration treatment (22 patients) and 89.5% after ASCT (19 patients).

“This difference in MRD-negative rate looks striking,” Yong said. “But I would draw your attention to the relatively small patient numbers in these groups.”

As for survival outcomes, Yong noted that the Kyprolis-based regimen was not non-inferior to ASCT. At a median follow-up of 37.5 months, two-year progression-free survival rate in the ASCT group was 76% compared with 70% in the Kyprolis-based short duration group. Patients in the ASCT group have not yet reached a median progression-free survival, whereas the median progression-free survival in the short-duration treatment group is 3.4 years.

Following randomization, patients who were minimal residual disease-negative following stem cell collection had similar progression-free survival rates in the ASCT and short-duration groups.

Yong noted that induction with the Kyprolis-based regimen produced deep responses in patients with a 24.3% minimal residual disease-negative rate. Additionally, VGPR rates were similar between the ASCT and short duration treatment groups. However, the minimal residual disease-negative rate was higher following ASCT (53%) than the short duration treatment (35.8%).

“High-risk patients have inferior (progression-free survival) compared to standard risk patients but in neither of these genetic risk groups is there evidence that ASCT is more effective than (Kyprolis-based short-duration treatment),” she concluded. “Patients who are (minimal residual disease)-positive at randomization may derive more benefit from ASCT than from (short-duration treatment).”

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

Articles

The study’s lead author noted that a survival outcome, along with other results, was similar among the two groups.

Kyprolis-Based Regimen Induces Similar Results as Autologous Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma

Patients with aggressive relapsed or refractory B-cell non-Hodgkin lymphoma achieved significant responses to treatment with mosunetuzumab plus Polivy (polatuzumab vedotin), according to study results.

The findings, which were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, also demonstrated that the combination was safe in this patient population.

Previously, data have shown that treatment with mosunetuzumab alone 

was safe and effective in treating relapsed/refractory non-Hodgkin lymphoma

Additionally, recent results from a mouse model indicated that combining mosunetuzumab with Polivy conferred increased efficacy compared to either agent alone.

“These data supported a phase 1b/2 open-label multicenter trial of M-Pola for relapsed-refractory B-NHL,” lead study author Dr. Elizabeth Budde, of City of Hope, said during a presentation of the study results.

Here, Budde presented early clinical data from the dose-finding phase 1b cohort comprised of 22 patients (median age, 70 years; 50% men) with either relapsed/refractory follicular lymphoma (FL) or aggressive NHL, including diffuse large B-cell lymphoma (12 patients), transformed FL (4 patients) and FL grade 3b (3 patients).

Patients were excluded from enrollment onto trial if they had received CD20-directed bispecific antibodies, as well as immunochemotherapy within four weeks of the first dose of study drug or radiotherapy within two weeks of first dose of study drug.

Determining a recommended phase 2 dose of study drug served as this cohort’s main goal.

Patients had received a median three prior lines of therapy (range, 1-10), and seven patients had previously received treatment with a CAR-T cell therapy.

At a median follow-up of 9.6 months, all patients experienced at least one side effect. Neutropenia (low white blood cell count) and nausea (40.9%, respectively), as well as fatigue and diarrhea (36.4%, respectively) were the most common treatment-related side effects. Two patients experienced a fatal event — one because of sudden cardiac death and another because of respiratory failure. However, the study authors noted that those deaths were not considered related to treatment. Of note, side effects led to dose modification among eight patients and treatment discontinuation in three patients.

Two cases of cytokine release syndrome (release of cytokines into the blood from immune cells affected by treatment) occurred during the course of therapy; however, both were considered non-severe and were treated without the need of the immunosuppressive drug Actemra (tocilizumab), admission to the ICU or use of vasopressors (used to raise low blood pressure).

Importantly, Budde noted, there were no side effects of neurotoxicity.

More than half of the patient population (54.5%) achieved a complete response to treatment.

“(Mosunetuzumab with polatuzumab vedotin) showed promising efficacy in patients with relapsed/refractory NHL with predominantly aggressive histology,” Budde concluded. “Complete response rate was seen in … patients who failed prior CAR Ts and patients with high-grade lymphoma.”

The phase 2 expansion cohort in patients with relapsed/refractory DLBCL is currently ongoing.

Treatment with a novel combination therapy was associated with increased efficacy among patients with aggressive relapsed or refractory B-cell non-Hodgkin lymphoma and was also well tolerated.

Novel Combo Therapy Shows Promise in Certain Patients With Non-Hodgkin Lymphoma

Treatment with a single infusion of the novel CAR-T cell therapy ciltacabtagene autoleucel (cilta-cel) induced early and deep responses in a group of patients with relapsed/refractory multiple myeloma, according to results of a phase 2 study.

The findings, which were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated that a single-infusion of the CAR-T cell therapy resulted in an overall response rate (which includes a partial response or better) of 95% with a stringent complete response rate of 75%, and a very good partial response rate or better of 85%.

Cilta-cel, formerly JNJ-68284528, is a second-generation CAR-T cell therapy with two BCMA-targeting, single-domain antibodies designed to confer avidity. Previous data that were published from the phase 1b/2 CARTITUDE-1 trial demonstrated that single infusion of cilta-cel was associated with deep and durable response among heavily pretreated patients with relapsed/refractory disease.

Measuring minimal residual disease negativity, or the small number of cancer cells in the body after cancer treatment, was the main goal of the study. Other goals included assessing overall response rate, duration of response, as well as time and duration of minimal residual disease negativity and incidence and severity of side effects.

The study comprised 20 patients (median age, 60 years; 65% men) who were either refractory to treatment with the chemotherapy lenalidomide or relapsed after one to three prior lines of treatment. One of the patients was treated in an outpatient setting.

Twelve of the patients had received fewer than three lines of prior therapy, and the remaining individuals received three prior lines of therapy.

All the patients had been previously treated with a proteasome inhibitor, an immunomodulatory drug and the steroid dexamethasone. Almost all (95%) of the patients were exposed to alkylating agents, and 65% received treatment with Darzalex (daratumumab).

As of the data cutoff of January 2021, four evaluable patients achieved minimal residual disease negativity.

Blood-related side effects that occurred in 20% or more of the patients included neutropenia (95%), thrombocytopenia (80%), anemia (65%), lymphopenia (60%) and leukopenia (55%). Moreover, cytokine release syndrome (which involves the cytokines overstimulating the immune system so that it attacks healthy organs) occurred in 85% of patients, of which 10% were considered serious or severe.

“The safety profile was manageable, including in the one patient that was treated in the outpatient setting,” said study author Dr. Mounzer E. Agha, director of the Mario Lemieux Center for Blood Cancers and clinical director of Hematopoietic Stem Cell Transplantation at the UPMC Hillman Cancer Center in Pittsburgh, during a recorded presentation of the data. “There were no cases of movement and neurocognitive adverse effects.”

Agha noted that one death occurred 100 days after the infusion of cilta-cel due to COVID-19 infection and was assessed as treatment-related by the investigators.

“Early and deep responses were observed with a single infusion of cilta-cel in lenalidomide refractory patients with multiple myeloma, who received one-to three prior lines of therapy,” he concluded.

The CAR-T cell therapy is being evaluated in other cohorts of the CARTITUDE-2 in earlier line settings, as well as in the phase 3 CARTITUDE-4 study in patients with one to three prior lines of therapy.

A single infusion of a novel CAR-T cell therapy was associated with early and deep responses to treatment among a certain group of patients with multiple myeloma.

Novel CAR-T Cell Therapy Produces Early and Deep Responses in Certain Patients with Multiple Myeloma

Kim Thiboldeaux refers to herself as a world traveler. She has visited all seven continents, been to more than 50 countries and has seen all 50 states. During those travels, Thiboldeaux, who is the executive chair of the 

nonprofit organization Cancer Support Community

, has interacted with thousands of people living with cancer.

After noticing a theme in her discussions with patients, their friends and families, Thiboldeaux decided to write “

.” In the book, Thiboldeaux provides a guide full of resources for anyone who may be affected by cancer — including patients, caregivers and family members.

“Whenever I (travel), I always have a good guidebook in hand,” she said in an interview with CURE®. “I hope this will be a guidebook or roadmap for patients.”

Here, Thiboldeaux talks about some of the topics that aren’t always discussed during the cancer journey, as well as why the book includes essays from patients including celebrities, and more.

CURE®: Why was it so important to put this book together?

 Over the past 20 years, I have spoken to thousands of (patients with) cancer and their family members and loved ones, and I found in these conversations certain themes emerge. I found that I was sharing the same information, same advice and tips. And it just seemed to make sense to put it all in one place in an easy to use format, so that anyone facing a cancer diagnosis has this book, “Your Cancer Road Map.”

Also, there have been so many advances, especially in the past decade, when it comes to cancer diagnosis, treatment and care. I wanted to make sure that folks had the most up-to-date information on facing a diagnosis.

What are some of the main takeaways from the book?

I remember some years ago, speaking to a woman in Virginia who had just been diagnosed with cancer, and I remember she said to me, “I don't know what my outcome is gonna be, but come what may, I want to feel confident in my decisions.” That conversation always stuck with me. My hope is that the book will help people feel more confident as they face a myriad of decisions, when diagnosed with cancer, whether it's around getting the right genetic and genomic testing, understanding insurance, understanding finances, talking to your kids about cancer, I want this book to help folks know that they really don't have to face cancer alone.

Why put together a book that is not just for one specific group, but rather everyone who may be involved in someone’s cancer journey?

People find the Cancer Support Community at different points in their cancer journey. I wanted folks to be able to kind of jump into this book at any time. No matter where they are in the journey, they could pick it up, flip to the table of contents and go straight to any chapter or topic that's really relevant to them. But we wanted to follow that full continuum from diagnosis, through either post treatment, survivorship or end of life. We also know that cancer doesn't just affect the individual or the patient, it affects family, friends, coworkers, neighbors … everyone around you; this book is as much for those people surrounding the patient as it is for the patient.

The book touches upon topics such as finance, sexual health and hospice care among others. What topics do you hope people pay more attention to than they normally would?

There are a number of areas where I see patients often have misconceptions. One of those areas, for example, is clinical trials. I think sometimes patients think that they'll get a placebo in a cancer treatment trial, which is almost never the case. So, I want folks to think about trials in a different way and really dig in and understand what they are. People also think you only go on a trial as a last-ditch effort, which is not the case.

Another critical area these days is genomic or biomarker testing. It is critical now that folks get the right biomarker testing because getting the right testing will inform the right treatment at the right time. We still find that patients don't quite understand it, (and) there's a lot of good information about that.

The last thing that I would ask people to think about is their emotional wellbeing. We know that cancer brings distress, anxiety (and) depression. Those things are very normal in a cancer diagnosis. But I think sometimes people neglect them, (and) I want them to know that those are normal feelings to experience. And there are lots of ways to address that. Maybe they want to participate in a support group, maybe they just want to go to a one-on-one with a private therapist, maybe they want to reach into their faith community for the emotional support that they find they may need. But I want them to know that that's normal.

The book includes personal stories from the average person, as well as celebrities such as Joan Lunden and ESPN’s Holly Rowe. Why was it important to include these essays, and what are you hoping people take away from these stories?

I always say that cancer is the great equalizer. It doesn't care if you're an athlete, or a celebrity or a journalist or a businessperson. Cancer shows no regard for age, for race, for gender, geography or socioeconomic status. (The) personal stories and experiences in the book, in some ways, make cancer a little less scary. It gives people the inspiration to face a cancer diagnosis empowered. And if you think about some of these folks who did face cancer in the spotlight, I'm hoping it brings (people) inspiration. And, in their stories and essays, they share some tools and practical tips when facing a cancer diagnosis.

What are you hoping people walk away with after reading the book?

I really hope that people walk away feeling empowered and confident. I also want folks to understand that there's no bad question, no wrong question, no stupid question. This is your life, (and) everything's on the table.

I hope they read through these chapters and get into some of the detail on some of these topics and go, “Oh, yeah, that was a question I had, but I never really wanted to ask anybody about it.” I hope that it does that for folks, and that it inspires them to be their own best advocate in their health care. And I also hope they see the resources outlined in the book and realize that there are a ton of resources available to help them. There's a whole community that's out there standing with you, standing there to support you, and I tried to include as many of those as I could in this book.

This interview has been edited for clarity and conciseness.

It is important to help people feel more confident as they face many decisions during their cancer journey and provide them with resources to show them that they don’t have to face the disease alone.

Ryan McDonald

Kyprolis-Based Regimen Induces Similar Results as Autologous Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma

Novel Combo Therapy Shows Promise in Certain Patients With Non-Hodgkin Lymphoma

Novel CAR-T Cell Therapy Produces Early and Deep Responses in Certain Patients with Multiple Myeloma

Empowering People to Navigate Their ‘Cancer Road Map’

Latest News