Lung Metastases Imaging: Practice Essentials, Radiography, Computed Tomography
Alencar Discusses Treatment Choices After Early Relapse Of DLBCL
During a Case-Based Roundtable® event, Alvaro Jose Alencar, MD, moderated a peer discussion on treatment options for a patient with diffuse large B-cell lymphoma whose disease relapsed eight months after completion of standard R-CHOP.
Alvaro Jose Alencar, MD (MODERATOR)
Associate Professor of Clinical Medicine
Chief Medical Officer
University of Miami
Sylvester Comprehensive Cancer Center
Miami, FL
EVENT REGION North Carolina and South Carolina
PARTICIPANT LIST Anusha Madadi, MDNiyati Nathwani, MDAlexandra Stefanovic, MDLouay Hanna, MDGary Thomas, MDMatthew McKinney, MDMaurizio Bendandi, MDCharles Kuzma, MDXuezhong Yang, MD
MADADI: If they relapse in less than 12 months or have primary refractory disease, they are considered high-risk patients with poor prognosis. If the patient is eligible for CAR [chimeric antigen receptor] T-cell therapy, this would be the ideal setting for CAR T-cell therapy demonstrating better overall response rate and PFS [progression-free survival] compared with stem cell transplant.
NATHWANI: I would say less than 12 months definitely would be early relapse and they do worse, and now that CAR T-cell therapy is [available] for the second line, at least for us in a small community practice, we end up referring these patients to the closest CAR T-cell therapy center for second line.
STEFANOVIC: Sometimes the [progression] of the disease is so fast that we have to bridge them before we can get them to CAR T-cell therapy, and some patients do not survive until they can get CAR T-cell therapy, particularly if they don't respond to the bridge.
ALENCAR: Initially, primary refractory disease was defined as 12 months from the initial diagnosis, and that's probably the more accurate way. But to make it easier for eligibility…the studies defined the eligibility based on the end of the therapy, so [primary refractory would be] 12 months from the end of induction. Those patients are hard to treat. If you remember the SCHOLAR data with patients with refractory disease, these patients have an extremely poor survival and it's generally less than 6 months, extremely refractory to cytotoxic therapy.1
One thing that is very important is that you not only have primary refractory but those who progress on first-line anthracycline-based therapy. Those patients tend to do even worse. Today we know that cellular therapy is the best intervention that we have for these patients. But to Dr Stefanovic's point, the issue is that a lot of times these patients are either progressing too fast or…sometimes you don't have a CAR T-cell program close to you, so patients cannot get CAR T-cell therapy early enough. A lot of times you will be using bridging therapies or alternative approaches. In this setting… what do you usually prefer to use as a bridging option or [to] try to control the disease?
HANNA: Especially when patients relapse within a year, I look at those as chemotherapy refractory. We have to get them on something more targeted or a different mechanism of action other than chemotherapy. We have quite a few options; you can make a case that you can use pola-BR [polatuzumab vedotin (Polivy), bendamustine, rituximab]. That's one option. The other option is anti-CD19 plus lenalidomide [Revlimid].
ALENCAR: [Not only] are they chemotherapy refractory, but chemotherapy will also start impacting your marrow function and start [causing] complications with cytopenias after CAR T-cell therapy. Not only [is there] the issue with the myelosuppression but also the lymphopenia and the lymphotoxicity from some chemotherapy agents, such as bendamustine. I agree that in this setting, chemotherapy is not the best option, and we will end up using alternative options, as you mentioned, polatuzumab-based therapy or tafasitamab [Monjuvi]–based therapies.
THOMAS: I usually check with the [cellular therapy physician] to whom I'm referring and get their advice on which regimen they would recommend in a situation like this. We've used tafasitamab/lenalidomide more than any other.
ALENCAR: Have you had any concerns with the targeting of CD19 prior to CAR T-cell therapy?
THOMAS: I don't have enough experience with it. I [must] rely on the physician to whom we're referring [the patient]. I would worry about it, but I don't know enough, as a general oncologist, whether that's important or not.
ALENCAR: There were recent data that were published in Blood, and it seems that tafasitamab prior to CAR T-cell therapy may populate the CD19 receptors that are not from the lymphoma and improve the efficacy of CAR T-cell therapy, which was completely opposite to what we initially believed: that by targeting CD19, you might decrease the efficacy of the targeting with CAR T-cell therapy.2 We tried to put together data from patients treated with anti-CD19 agents prior to CAR T-cell therapy, and it was just a small number of patients, but it seems that it's acceptable and does not seem to impact the efficacy of CAR T-cell therapy.3 Obviously, patients who require bridging are more complicated. Those are the ones whose disease is progressing, and CAR T-cell therapy tends to have a harder time having good efficacy in actively growing tumors. But tafasitamab/lenalidomide tends to be a very reasonable option. Is anyone concerned with polatuzumab as bridging, [especially] now that we're using more polatuzumab in first-line therapy?
MCKINNEY: Having done a lot of CAR T-cell therapy, the key is to line patients up for cell collection as soon as possible, and then you have different options for bridging them. I am gun-shy about using bendamustine immediately after cell collection; then you run into issues with not being able to manufacture cells. Axicabtagene ciloleucel [Yescarta] is…reliable, but I backed off after a couple of bad experiences doing that and then tried to use some milder bridging schemes.
My issue with doing tafasitamab/lenalidomide is it takes… 2 or 3 weeks just to get that approved through insurance and set it up. As a bridging regimen, it's a lot of work to get a patient to cell collection and then to do that. By the time they get loaded with tafasitamab, you're doing CAR T-cell therapy anyway. [I use] a variety of different bridging regimens, and maybe radiation. Your goal is just to temporize disease, so even R-ICE [rituximab, ifosfamide, carboplatin, etoposide phosphate] or some sort of platinum-based regimen [could be used].
These patients who have this primary refractory disease to R-CHOP or pola-R-CHP [polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride, prednisone], if they're rapidly progressing, are also patients you're not going to get to CAR T-cell therapy and they're probably going to pass away.
CASE UPDATE
The patient was referred to the nearest transplant and cellular therapy center for evaluation but opted not to pursue CAR T-cell therapy. The patient prefers to stay with his current care team but is still seeking further treatment. He wants to receive outpatient treatment due to lack of a support system.
DISCUSSION QUESTIONS
ALENCAR: This patient is not going to receive CAR T-cell therapy. What is the goal when you're treating like this? The patient [whose disease is] primary refractory is expected to have a difficult-to-control disease and will likely die from his disease. How do you use these factors to define the therapy?
BENDANDI: I would choose pola-BR precisely because collection is a moot point, and this is the last shot at a bit of chemotherapy. Bendamustine is not a miracle drug but is not terrible either in terms of the results. Polatuzumab was not added in the first line, so in the second line it's appropriate. We don't have any evidence that tafasitamab/ lenalidomide would be better or worse. The populations of patients [in the trials] resemble each other, but they're not comparable.
KUZMA: I would choose tafasitamab. I thought the data [show it is] less toxic with better chance of durable responses with a different novel mechanism of action than the chemotherapy that the patient already failed. The likelihood of this patient having a long-term response is greater with a tafasitamab regimen than with pola-BR, with that choice becoming more solidified with polatuzumab moving up to the frontline setting.
YANG: I think I'm still undecided at this point. My guess is for a patient like that, we'll probably circle through each line until they [receive] CAR T-cell therapy or bispecific. Otherwise, it's a matter of order.
MCKINNEY: I don't see any reason not to do tafasitamab/lenalidomide. My experience with pola-BR is it's hard to do more than 3 or 4 cycles in these patients, whereas tafasitamab/lenalidomide in the second line, if they're willing to come in for all the infusions for tafasitamab… that's a nice way to go. I have a ton of patients who are more than a year out for tafasitamab coming back, and it's a discussion about when we are going to stop doing this. The FDA label says you continue every 2 weeks. I don't have anyone who did 4 to 6 cycles of pola-BR and…they're coming back in remission doing fine.
ALENCAR: Do they stop because of progression, or do they stop because of toxicity?
MCKINNEY: I would say both.
ALENCAR: Do you take into consideration the schedule with the loading of the tafasitamab in the beginning? Does the fact that one is an infusion every 3 weeks and one has this weekly infusion [plus] a pill every day matter?
MCKINNEY: It's a discussion in the third line with loncastuximab tesirine [Zynlonta] vs tafasitamab. In older patients who don't want to come to the clinic very much, that's the downside. It's just a lot of infusions trying to keep patients on tafasitamab. That is less of a difference in the discussion for the schedule for pola-BR vs tafasitamab/ lenalidomide because if you describe [to patients that] you're going to get chemotherapy, you have to deal with those adverse events, and you may be back and you may be getting growth factor; [the schedule of tafasitamab] is less important for that distinction. But vs loncastuximab or bispecifics, that's where it comes up.
ALENCAR: Does the cell of origin make a difference? This patient had a non-GCB cell of origin.
STEFANOVIC: It does make a difference, and I think for non-GCB, lenalidomide is a great drug, either by itself or in combination with tafasitamab. Patients who live far away might not find it easy to come every week for the tafasitamab. But also lenalidomide lends itself to easy dose adjustments if needed for cytopenias. One can go down on the dose easily, and one can keep patients on both treatments. We don't have the same cumulative toxicities that we would see with polatuzumab or with bendamustine. For a patient who responds to a combination, it is a good option, and…it can keep the door open for the other third-line treatments that have great promise.
ALENCAR: Do you have any concern with the co-payments for the oral agent?
STEFANOVIC: With the lenalidomide, it's a question of delays with the patient going through the authorization and co-pay assistance. It can be up to 2 weeks, and tafasitamab by itself isn't that great. One needs the lenalidomide onboard to get a response there. That is a moment of anxiety where we sometimes wish we could get the treatment faster.
ALENCAR: If you get the tafasitamab approved but are still waiting on the lenalidomide, do you just get the tafasitamab started and you pick up with the lenalidomide whenever you can or do you wait until you have both in hand before you start?
STEFANOVIC: Ideally, one should have both. I have gone with tafasitamab and then started the lenalidomide after 2 weeks or so, but it is ideal to have both at the same time. I don't think the tafasitamab has great efficacy on its own.
CASE UPDATE
This patient is started on tafasitamab plus lenalidomide.
DISCUSSION QUESTION
THOMAS: I used it on one patient and the patient stayed in control of the disease for about probably a year, and they tolerated it very well.
ALENCAR: Were there any issues with toxicity, or tolerability, or problems that you have noticed in these patients? We discussed the schedule with the frequent infusions, the cytopenias, and kidney dysfunction.
KUZMA: I have run into some problems with myelosuppression that have led to lenalidomide dose modification.
ALENCAR: Did you drop the dose, or did you try to use some growth factors before that?
KUZMA: I dropped the dose.
ALENCAR: Did you start with 25 mg, or did you start already with a lower dose?
KUZMA: I've only used it a total of 3 times. Two times, I started with 25 mg. One time, due to frailties and comorbidities, I did start at 20 mg. But 2 of the 3 patients ended up at 15 mg.
ALENCAR: For those patients who had long-term disease control and you reach that point when, according to the study, you drop the lenalidomide and keep the tafasitamab, are you happy to drop the lenalidomide and keep the tafasitamab? Do you think you still need to keep the tafasitamab at that same frequency or do you get creative and start spreading it out?
MCKINNEY: I drop the lenalidomide. A year is enough. That seems [clearer] to me. I haven't thought about prolonging it. These patients will go another 6 to 12 months with tafasitamab, and I've had some discussions where we spread it out every 3 weeks. I have no real data to support that. I know there are different preparations of tafasitamab out there in trials investigating that. I just have a discussion with the patient.
ALENCAR: Do they get tired of coming in every 2 weeks?
MCKINNEY: It's a long time for every-2-week infusions to go beyond 2 years.
ALENCAR: The company is looking into alternative schedules and trying to work with patients because it's very tough after a year to come every 2 weeks to get infusions. But you have those patients who have excellent responses and it's very hard to just abandon a drug that seems to be working [in] these patients with tough-to-treat [disease] and a finite number of options.
REFERENCES: 1. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. Doi:10.1182/blood-2017-03-769620 2. Sakemura RL, Manriquez Roman C, Horvei P, et al. CD19 occupancy with tafasitamab increases therapeutic index of CART19 cell therapy and diminishes severity of CRS. Blood. 2024;143(3):258-271. Doi:10.1182/blood.2022018905 3. Veeraputhiran M, Mehta A, Alencar AJ, Modi D, Voorhees TJ, Narkhede M. Tafasitamab (TAFA) plus lenalidomide (LEN) prior to chimeric antigen receptor T-cell (CAR-T) therapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): case series of 8 patients. Blood. 2022;140(suppl 1):12089-12091. Doi:10.1182/blood-2022-158595Bristol Myers Squibb's CAR T Cell Therapy Breyanzi Approved By The U.S. Food And Drug Administration For Relapsed Or Refractory Follicular Lymphoma
PRINCETON, N.J.--(BUSINESS WIRE)--May 15, 2024--
Bristol Myers Squibb (NYSE: BMY) today announced the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Breyanzi® (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Breyanzi is also now included in the National Comprehensive Cancer Network (NCCN ® ) Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) for B-cell Lymphomas as a Category 2A recommendation for third-line and subsequent therapy for relapsed or refractory FL.*
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Product image for download (Photo: Bristol Myers Squibb)
In relapsed or refractory FL, Breyanzi is delivered as a one-time infusion** with a single dose containing 90 to 110 x 10 6 CAR-positive viable T cells. Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding Cytokine Release Syndrome (CRS), Neurologic Toxicities, and Secondary Hematological Malignancies.
" Breyanzi is a cornerstone of our cell therapy portfolio, providing a differentiated profile across a wide array of B-cell malignancies," said Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb. "Today's approval of Breyanzi for relapsed or refractory FL provides an option with potential for lasting remission in a one-time infusion and a safety profile that allows for administration and monitoring in both the inpatient and outpatient setting in an increasing number of certified treatment centers in the U.S."
Historically, FL has been considered an incurable disease, and patients frequently relapse following front-line therapy, with prognosis worsening after each subsequent relapse. Despite advances in treatment, there remains an unmet need for additional options that offer treatment-free intervals with durable, complete responses.
The Phase 2 TRANSCEND FL study included the largest primary analysis set of patients with relapsed or refractory FL of a clinical trial evaluating a CAR T cell therapy in this patient population. Based on the U.S. Prescribing Information (USPI), in patients treated with Breyanzi in the third-line plus setting and included in the primary efficacy analysis set (n=94), the overall response rate (ORR) was 95.7% (95% CI: 89.5-98.8). ORR was defined as the percentage of patients achieving a partial or complete response per Lugano criteria as assessed by an Independent Review Committee (IRC). The complete response (CR) rate was 73.4% (95% CI: 63.3-82.0) and required a negative bone marrow biopsy for confirmation. Responses were rapid and durable with a median time to response of one month (range: 0.6-3.3) and median duration of response (DOR) not reached (95% CI: 18.04-NR), with 80.9% of responders remaining in response at 12 months, and 77.1% of responders remaining in response at 18 months. Results from the primary analysis of TRANSCEND FL presented at the 2023 International Conference on Malignant Lymphoma showed an ORR of 97% (95% CI: 91.6-99.4; one-sided p<0.0001) in efficacy evaluable patients (n=101), with 94% of patients achieving a CR (95% CI: 87.5-97.8; one-sided p<0.0001).
"In the treatment of relapsed or refractory follicular lymphoma, patients often cycle through treatments with typically shorter responses with each new line of therapy. Those who have experienced early disease progression have notably poor prognosis," said M. Lia Palomba, M.D., TRANSCEND investigator and lymphoma and cell therapy specialist, Memorial Sloan Kettering Cancer Center. "The FDA approval of liso-cel for patients with relapsed or refractory FL is an important advancement in addressing an ongoing unmet need in the FL treatment paradigm, providing patients a new option that has shown remarkably high response rates and an established safety profile."
Breyanzi has exhibited a consistent safety profile and across clinical trials , any grade cytokine release syndrome (CRS) occurred in 53% of patients, including Grade > 3 CRS in 4% of patients. The median time to onset was 5 days (range: 1 to 63 days). Any grade neurologic events (NEs) occurred in 31% of patients, with Grade > 3 NEs occurring in 10% of patients. The median time to onset of NEs was 8 days (range: 1 to 63 days). The safety profile of Breyanzi allows for the option of outpatient treatment and management of patients. Patients in the TRANSCEND FL study were treated in the inpatient and outpatient setting.
"The lymphoma community has felt an urgent need for advancements in the treatment of relapsed or refractory follicular lymphoma," said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation. "The approval of Breyanzi offers patients a new and meaningful treatment option that provides hope for lasting remission, and we are grateful to those who have contributed to this exciting milestone for patients."
Bristol Myers Squibb offers various programs and resources to address the needs of patients and caregivers, and provides support that allows for access to therapies, including Breyanzi. Bristol Myers Squibb also supports the patient and physician treatment experience by providing Cell Therapy 360, a digital service platform, which optimizes access to relevant information, manufacturing updates, and patient and caregiver support.
* NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
** Treatment process includes leukapheresis, manufacturing, administration, and adverse event monitoring.
About TRANSCEND FL
TRANSCEND FL (NCT04245839) is an open-label, global, multicenter, Phase 2, single-arm study to determine the efficacy and safety of Breyanzi in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, including follicular lymphoma. The primary outcome measure is overall response rate, including best overall response of complete response or partial response as determined by an Independent Review Committee. Secondary outcome measures include complete response rate, duration of response, progression-free survival, and safety.
About FL
Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL) and the most common subtype of indolent NHL, accounting for 20 to 30 percent of all NHL cases. The average age of diagnosis for FL is 65 years of age. FL develops when white blood cells cluster together to form lumps in a person's lymph nodes or organs. It is characterized by periods of remission and relapse, and the disease becomes more difficult to treat after relapse or disease progression.
About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient's own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment.
Breyanzi is approved in the U.S. For the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy and received accelerated approval for the treatment of relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two prior lines of therapy. Breyanzi is also approved in Japan, the European Union (EU), and Switzerland for the second-line treatment or relapsed or refractory LBCL, and in Japan, the European Union, Switzerland, the UK and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy.
Bristol Myers Squibb's clinical development program for Breyanzi includes clinical studies in other types of lymphoma. For more information, visit clinicaltrials.Gov.
Indication
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.
Important Safety Information
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES
Cytokine Release Syndrome (CRS)
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. In clinical trials of BREYANZI which enrolled a total of 614 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 53% of patients, including Grade 3 or higher CRS in 4% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 98% of patients with median duration of 5 days (range: 1 to 37 days). The most common manifestations of CRS ( > 10%) were fever, hypotension, tachycardia, chills, hypoxia and headache.
Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.
Neurologic Toxicities
Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.
In clinical trials of BREYANZI, CAR T cell-associated neurologic toxicities occurred in 31% of patients, including > Grade 3 cases in 10% of patients. The median time to onset of neurotoxicity was 8 days (range: 1 to 63 days). Neurologic toxicities resolved in 87% of patients with a median duration of 8 days (range: 1 to 119 days). Of patients developing neurotoxicity, 81% also developed CRS.
The most common neurologic toxicities (≥ 5%) included encephalopathy, tremor, aphasia, headache, dizziness, and delirium.
CRS and Neurologic Toxicities Monitoring
Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.
BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:
Further information is available at www.BreyanziREMS.Com, or contact Bristol Myers Squibb at 1-866-340-7332.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).
Serious Infections
Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. In clinical trials of BREYANZI, infections of any grade occurred in 33% of patients, with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections in 4%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient who received four prior lines of therapy developed a fatal case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy four months after treatment with BREYANZI.
Febrile neutropenia developed after BREYANZI infusion in 8% of patients. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.
Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines. Avoid administration of BREYANZI in patients with clinically significant, active systemic infections.
Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. In clinical trials of BREYANZI, 26 of 29 patients with prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.
Prolonged Cytopenias
Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. In clinical trials of BREYANZI, Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 34% of patients, and included thrombocytopenia in 24%, neutropenia in 22%, and anemia in 7% of patients. Monitor complete blood counts prior to and after BREYANZI administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI. In clinical trials of BREYANZI, hypogammaglobulinemia was reported as an adverse reaction in 10% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 29% of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.
Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.
Secondary Malignancies
Patients treated with BREYANZI may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.
Effects on Ability to Drive and Use Machines
Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for developing altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks.
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS)
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis (IEC-HS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Three of 89 (3%) safety evaluable patients with R/R CLL/SLL developed IEC-HS. Time to onset of IEC-HS ranged from 7 to 18 days. Two of the 3 patients developed IEC-HS in the setting of ongoing CRS and 1 in the setting of ongoing neurotoxicity. IEC-HS was fatal in 2 of 3 patients. One patient had fatal IEC-HS and one had ongoing IEC-HS at time of death. IEC-HS is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of IEC-HS should be administered per current practice guidelines.
Adverse Reactions
The most common adverse reactions (incidence ≥ 30%) in:
Please see fullPrescribing Information, including Boxed WARNINGS andMedication Guide.
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PUB: 05/15/2024 08:57 PM/DISC: 05/15/2024 08:57 PM
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BMS CAR-T Therapy Wins FDA Approval For Expanded Use In Follicular Lymphoma
Pictured: Bristol Myers Squibb office in California/iStock, hapabapa
The FDA on Wednesday approved the label expansion of Bristol Myers Squibb's CAR-T cell therapy Breyanzi (lisocabtagene maraleucel) for the treatment of patients with relapsed or refractory follicular lymphoma.
Wednesday's approval, which expands the use of Breyanzi in patients who had undergone at least two prior lines of systemic therapy, was granted under the FDA's accelerated pathway based on response data. To keep the approval, BMS will need to confirm Breyanzi's clinical benefit in this indication through a Phase III confirmatory study.
Bryan Campbell, head of commercial, cell therapy at BMS, in a statement called Breyanzi a "cornerstone" of the pharma's cell therapy portfolio, adding that its expansion into relapsed or refractory follicular lymphoma (FL) gives patients a treatment option "with potential for lasting remission in a one-time infusion."
Designed to be administered intravenously, Breyanzi is a CD19-directed CAR-T cell therapy that works by targeting B cells. Once bound to the CD19 surface protein, Breyanzi can proliferate and trigger the secretion of proinflammatory cytokines and induce cell death in cancer cells.
Breyanzi was first approved in February 2021 for the treatment of relapsed or refractory large B-cell lymphoma. In March 2024, the CAR-T therapy picked up an approval for small lymphocytic leukemia and chronic lymphocytic leukemia.
Wednesday's label expansion was backed by data from the Phase II TRANSCEND FL study, a single-arm, open-label trial that enrolled more than 210 patients with relapsed or refractory FL or marginal zone lymphoma. Results showed that treatment with Breyanzi resulted in a 95.7% overall response rate, with a complete response rate of 73.4%.
Response to treatment was rapid, with a median onset of one month. Median duration of response was not yet reached at the time of the analysis and 80.9% of patients still showed treatment response at 12 months.
The FDA has another upcoming decision date for Breyanzi, on May 31, 2024, for refractory mantle cell lymphoma.
Like all commercially available CAR-T therapies, Breyanzi carries a boxed warning for the risk of secondary hematological malignancies. The FDA in November 2023 revealed that it detected and was looking into cases of secondary cancers in patients treated with CAR-T therapies. In January 2024, the regulator published more details regarding these adverse events, noting that it had found the CAR transgene in three cases of these secondary cancers.
Breyanzi's boxed warning also warns against cytokine release syndrome and neurologic toxicities.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.Com or tristan.Manalac@biospace.Com.
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