Bristol Myers Squibb Presents New Information at ASH 2023 Demonstrating Scientific Profit Throughout B-cell Malignancies with Breyanzi as a Second-Line Remedy in Excessive-Threat Follicular Lymphoma and in Relapsed or Refractory Persistent Lymphocytic Leukemia

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Affected person-reported outcomes (PROs) from TRANSCEND FL are additionally being introduced ( Oral Presentation #668), representing the primary disclosure of PRO information for a CAR T cell remedy in relapsed or refractory FL. Based mostly on an exploratory evaluation, the vast majority of sufferers with second- or third-line relapsed or refractory FL reported clinically vital enhancements in high quality of life, illness signs, and functioning after being handled with Breyanzi. These receiving Breyanzi within the second-line setting typically demonstrated higher and quicker significant enhancements in most major domains, in comparison with those that acquired Breyanzi within the third-line setting, together with function and cognitive functioning, fatigue, ache, and Useful Evaluation of Most cancers Remedy Lymphoma scores.

Outcomes from the third-line-plus therapy cohort of TRANSCEND FL had been beforehand introduced on the 2023 Worldwide Convention on Malignant Lymphoma in June 2023.

Outcomes from TRANSCEND CLL 004
TRANSCEND CLL 004 is the primary pivotal, multicenter examine of a CD19-directed CAR T cell remedy for sufferers with relapsed or refractory persistent lymphocytic leukemia (CLL) after development on a BTK inhibitor (BTKi) and BCL-2 inhibitor (BCL2i). The examine included a broad inhabitants of sufferers with relapsed or refractory CLL or small lymphocytic leukemia (SLL) with excessive unmet want who had acquired at the least two prior strains of remedy, together with a BTKi (n=118), to be handled with Breyanzi. Outcomes from the first evaluation of TRANSCEND CLL 004, with a median follow-up of 21.1 months, had been beforehand introduced on the 2023 American Society of Scientific Oncology Annual Assembly in June 2023.

With a longer-term median (vary) follow-up of 23.5 months (0.4-59.6) within the prespecified major efficacy evaluation set (PEAS; n=50), which consisted of a subset of sufferers who had skilled illness development following therapy with a BTKi and failure of BCL2i-based regimens and who had been handled with the goal dose of 100 x 10⁶ CAR-positive viable T-cells of Breyanzi, sufferers derived statistically vital CR price of 20% (95% CI: 10.0-33.7), the examine’s major endpoint.

The excessive charges of undetectable minimal residual illness (uMRD) noticed with Breyanzi had been maintained with longer-term follow-up, with a uMRD price 64% within the blood (95% CI: 45.2-77.1) and 60% within the bone marrow (95% CI: 45.2-73.6). The ORR elevated to 44% (95% CI: 30.0-58.7), with a median (vary) DOR of 35.3 months (11.01-NR). One affected person who had a finest total response of partial response on the major evaluation skilled a deepening of response at 18 months, reaching a CR with none extra remedy. Of 9 sufferers who had achieved a CR at major evaluation, 8 had ongoing CRs and one accomplished the examine with the final evaluation as a CR.

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“For sufferers with relapsed or refractory CLL, present therapy choices hardly ever present full responses, and sturdiness of response is restricted,” mentioned Tanya Siddiqi, M.D., lead investigator and affiliate professor within the Division of Hematology and Hematopoietic Cell Transplantation and Director of the CLL program at Metropolis of Hope Nationwide Medical Heart. “With long-term follow-up from TRANSCEND CLL 004, the whole and lasting responses achieved with liso-cel are unprecedented on this affected person inhabitants, with a deepening of responses noticed over time and a manageable and predictable security profile. Based mostly on these outcomes, liso-cel has the potential to be a big advance within the therapy of relapsed or refractory CLL.”

Amongst all handled sufferers (n=118), Breyanzi exhibited a manageable security profile, with any grade CRS noticed in 85% of sufferers, with Grade 3 CRS occurring in 8% of sufferers and no Grade 4/5 CRS reported. Any grade NEs had been reported in 45% of sufferers, with Grade 3 NEs occurring in 18% of sufferers, Grade 4 NEs occurring in 1% of sufferers, and no Grade 5 NEs reported.

About TRANSCEND FL
TRANSCEND FL (NCT04245839) is an open-label, world, multicenter, Section 2, single-arm examine to find out the efficacy and security of Breyanzi in sufferers with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, together with follicular lymphoma and marginal zone lymphoma. The first consequence measure is total response price. Secondary consequence measures embody full response price, length of response, and progression-free survival.

About TRANSCEND CLL 004
TRANSCEND CLL 004 (NCT03331198) is a Section 1/2 open-label, single-arm, multicenter examine evaluating Breyanzi in sufferers with relapsed or refractory persistent lymphocytic leukemia or small lymphocytic lymphoma. The Section 1 dose escalation portion of the examine assessed the protection and really helpful dose for the next Section 2 growth cohort. The Section 2 portion of the examine is evaluating Breyanzi on the really helpful dose from the Section 1 monotherapy arm. The first endpoint of the Section 2 portion of the examine is full response price, together with full remission with incomplete bone marrow restoration, based mostly on impartial evaluation committee in accordance with the Worldwide Workshop on Persistent Lymphocytic Leukemia (iwCLL) 2018 tips.

About FL
Follicular lymphoma (FL) is the second most typical, slow-growing type of non-Hodgkin lymphoma (NHL), accounting for 20 to 30 % of all NHL circumstances. Most sufferers with FL are over 50 years of age when they’re recognized. FL develops when white blood cells cluster collectively to type lumps in an individual’s lymph nodes or organs. It’s characterised by durations of remission and relapse, and the illness turns into tougher to deal with after relapse or illness development.

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About CLL and SLL
Persistent lymphocytic leukemia (CLL) is likely one of the most typical sorts of leukemia in adults. In CLL, too many blood stem cells within the bone marrow change into irregular lymphocytes, and these irregular cells have problem preventing infections. Because the variety of irregular cells grows, there may be much less room for wholesome white blood cells, purple blood cells and platelets. Small lymphocytic lymphoma (SLL) additionally impacts the lymphocytes, with most cancers cells discovered largely within the lymph nodes. Whereas there are a number of therapies obtainable for CLL and SLL, there’s a want for extra efficient therapies as there is no such thing as a normal of look after relapsed or refractory CLL or SLL after prior remedy with focused brokers. Sufferers with relapsed or refractory illness have restricted therapy choices and customarily expertise shorter durations of response with every subsequent therapy.

About Breyanzi
Breyanzi is a CD19-directed CAR T cell remedy with a 4-1BB costimulatory area, which reinforces the growth and persistence of the CAR T cells. Breyanzi is made out of a affected person’s personal T cells, that are collected and genetically reengineered to change into CAR T cells which are then delivered by way of infusion as a one-time therapy.

Breyanzi is authorized within the U.S., Japan and Europe for the second-line therapy of relapsed or refractory LBCL, and in Japan, Europe, Switzerland, and Canada for relapsed and refractory LBCL after two or extra strains of systemic remedy. Bristol Myers Squibb’s scientific improvement program for Breyanzi contains scientific research in earlier strains of therapy for sufferers with relapsed or refractory LBCL and different sorts of lymphoma and leukemia. For extra info, go to clinicaltrials.gov.

U.S. Vital Security Info and Indication
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the therapy of grownup sufferers with giant B-cell lymphoma (LBCL), together with diffuse giant B-cell lymphoma (DLBCL) not in any other case specified (together with DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, major mediastinal giant B-cell lymphoma, and follicular lymphoma grade 3B, who’ve:

• refractory illness to first-line chemoimmunotherapy or relapse inside 12 months of first-line chemoimmunotherapy; or
• refractory illness to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and usually are not eligible for hematopoietic stem cell transplantation (HSCT) resulting from comorbidities or age; or
• relapsed or refractory illness after two or extra strains of systemic remedy.

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Limitations of Use: BREYANZI isn’t indicated for the therapy of sufferers with major central nervous system lymphoma.

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

• Cytokine Launch Syndrome (CRS), together with deadly or life-threatening reactions, occurred in sufferers receiving BREYANZI. Don’t administer BREYANZI to sufferers with energetic an infection or inflammatory issues. Deal with extreme or life-threatening CRS with tocilizumab with or with out corticosteroids.
• Neurologic toxicities, together with deadly or life-threatening reactions, occurred in sufferers receiving BREYANZI, together with concurrently with CRS, after CRS decision or within the absence of CRS. Monitor for neurologic occasions after therapy with BREYANZI. Present supportive care and/or corticosteroids as wanted.
• BREYANZI is accessible solely by way of a restricted program underneath a Threat Analysis and Mitigation Technique (REMS) referred to as the BREYANZI REMS.

Cytokine Launch Syndrome (CRS)
Cytokine launch syndrome (CRS), together with deadly or life-threatening reactions, occurred following therapy with BREYANZI. Amongst sufferers receiving BREYANZI for LBCL (N=418), CRS occurred in 46% (190/418), together with ≥ Grade 3 CRS (Lee grading system) in 3.1% of sufferers.

In sufferers receiving BREYANZI after two or extra strains of remedy for LBCL, CRS occurred in 46% (122/268), together with ≥ Grade 3 CRS in 4.1% of sufferers. One affected person had deadly CRS and a couple of had ongoing CRS at time of loss of life. The median time to onset was 5 days (vary: 1 to fifteen days). CRS resolved in 98% with a median length of 5 days (vary: 1 to 17 days).

In sufferers receiving BREYANZI after one line of remedy for LBCL, CRS occurred in 45% (68/150), together with Grade 3 CRS in 1.3% of sufferers. The median time to onset was 4 days (vary: 1 to 63 days). CRS resolved in all sufferers with a median length of 4 days (vary: 1 to 16 days).

The most typical manifestations of CRS (≥10%) included fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%).

Critical occasions that could be related to CRS embody cardiac arrhythmias (together with atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar harm, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

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Be certain that 2 doses of tocilizumab can be found previous to infusion of BREYANZI.

Of the 418 sufferers who acquired BREYANZI for LBCL, 23% acquired tocilizumab and/or a corticosteroid for CRS, together with 10% who acquired tocilizumab solely and a couple of.2% who acquired corticosteroids solely.

Neurologic Toxicities
Neurologic toxicities that had been deadly or life-threatening, together with immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following therapy with BREYANZI. Critical occasions together with cerebral edema and seizures occurred with BREYANZI. Deadly and severe circumstances of leukoencephalopathy, some attributable to fludarabine, additionally occurred.

In sufferers receiving BREYANZI after two or extra strains of remedy for LBCL, CAR T cell-associated neurologic toxicities occurred in 35% (95/268), together with ≥ Grade 3 in 12% of sufferers. Three sufferers had deadly neurologic toxicity and seven had ongoing neurologic toxicity at time of loss of life. The median time to onset of neurotoxicity was 8 days (vary: 1 to 46 days). Neurologic toxicities resolved in 85% with a median length of 12 days (vary: 1 to 87 days).

In sufferers receiving BREYANZI after one line of remedy for LBCL, CAR T cell-associated neurologic toxicities occurred in 27% (41/150) of sufferers, together with Grade 3 circumstances in 7% of sufferers. The median time to onset of neurologic toxicities was 8 days (vary: 1 to 63 days). The median length of neurologic toxicity was 6 days (vary: 1 to 119 days).

In all sufferers mixed receiving BREYANZI for LBCL, neurologic toxicities occurred in 33% (136/418), together with ≥ Grade 3 circumstances in 10% of sufferers. The median time to onset was 8 days (vary: 1 to 63), with 87% of circumstances creating by 16 days. Neurologic toxicities resolved in 85% of sufferers with a median length of 11 days (vary: 1 to 119 days). Of sufferers creating neurotoxicity, 77% (105/136) additionally developed CRS. The most typical neurologic toxicities (≥ 5%) included encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%), and delirium (5%).

CRS and Neurologic Toxicities Monitoring
Monitor sufferers each day for at the least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for indicators and signs of CRS and neurologic toxicities and assess for different causes of neurological signs. Monitor sufferers for indicators and signs of CRS and neurologic toxicities for at the least 4 weeks after infusion and deal with promptly. On the first signal of CRS, institute therapy with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Handle neurologic toxicity with supportive care and/or corticosteroid as wanted. Counsel sufferers to hunt rapid medical consideration ought to indicators or signs of CRS or neurologic toxicity happen at any time.

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BREYANZI REMS
Due to the danger of CRS and neurologic toxicities, BREYANZI is accessible solely by way of a restricted program underneath a Threat Analysis and Mitigation Technique (REMS) referred to as the BREYANZI REMS. The required parts of the BREYANZI REMS are:

• Healthcare amenities that dispense and administer BREYANZI should be enrolled and adjust to the REMS necessities.
• Licensed healthcare amenities should have on-site, rapid entry to tocilizumab.
• Be certain that a minimal of two doses of tocilizumab can be found for every affected person for infusion inside 2 hours after BREYANZI infusion, if wanted for therapy of CRS.
• Licensed healthcare amenities should make sure that healthcare suppliers who prescribe, dispense, or administer BREYANZI are skilled on the administration of CRS and neurologic toxicities.

Additional info is accessible at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions
Allergic reactions could happen with the infusion of BREYANZI. Critical hypersensitivity reactions, together with anaphylaxis, could also be resulting from dimethyl sulfoxide (DMSO).

Critical Infections
Extreme infections, together with life-threatening or deadly infections, have occurred in sufferers after BREYANZI infusion.

In sufferers receiving BREYANZI for LBCL, infections of any grade occurred in 36% with Grade 3 or larger infections occurring in 12% of all sufferers. Grade 3 or larger infections with an unspecified pathogen occurred in 7%, bacterial infections occurred in 4.3%, viral infections in 1.9% and fungal infections in 0.5%.

Febrile neutropenia developed after BREYANZI infusion in 8% of sufferers with LBCL. Febrile neutropenia could also be concurrent with CRS. Within the occasion of febrile neutropenia, consider for an infection and handle with broad spectrum antibiotics, fluids, and different supportive care as medically indicated.

Monitor sufferers for indicators and signs of an infection earlier than and after BREYANZI administration and deal with appropriately. Administer prophylactic antimicrobials in accordance with normal institutional tips.

Keep away from administration of BREYANZI in sufferers with clinically vital energetic systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some circumstances leading to fulminant hepatitis, hepatic failure, and loss of life, can happen in sufferers handled with medicine directed in opposition to B cells.

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In sufferers who acquired BREYANZI for LBCL, 15 of the 16 sufferers with a previous historical past of HBV had been handled with concurrent antiviral suppressive remedy. Carry out screening for HBV, HCV, and HIV in accordance with scientific tips earlier than assortment of cells for manufacturing. In sufferers with prior historical past of HBV, contemplate concurrent antiviral suppressive remedy to forestall HBV reactivation per normal tips.

Extended Cytopenias
Sufferers could exhibit cytopenias not resolved for a number of weeks following lymphodepleting chemotherapy and BREYANZI infusion.

Grade 3 or larger cytopenias continued at Day 29 following BREYANZI infusion in 36% of sufferers with LBCL and included thrombocytopenia in 28%, neutropenia in 21%, and anemia in 6%.

Monitor full blood counts previous to and after BREYANZI administration.

Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can happen in sufferers receiving therapy with BREYANZI.

In sufferers receiving BREYANZI for LBCL, hypogammaglobulinemia was reported as an antagonistic response in 11% of sufferers. Hypogammaglobulinemia, both as an antagonistic response or laboratory IgG degree beneath 500 mg/dL after infusion, was reported in 28% of sufferers.

Monitor immunoglobulin ranges after therapy with BREYANZI and handle utilizing an infection precautions, antibiotic prophylaxis, and immunoglobulin alternative as clinically indicated.

Reside vaccines: The security of immunization with reside viral vaccines throughout or following BREYANZI therapy has not been studied. Vaccination with reside virus vaccines isn’t really helpful for at the least 6 weeks previous to the beginning of lymphodepleting chemotherapy, throughout BREYANZI therapy, and till immune restoration following therapy with BREYANZI.

Secondary Malignancies
Sufferers handled with BREYANZI could develop secondary malignancies. Monitor lifelong for secondary malignancies. Within the occasion {that a} secondary malignancy happens, contact Bristol-Myers Squibb at 1-888-805-4555 for reporting and to acquire directions on assortment of affected person samples for testing.

Results on Potential to Drive and Use Machines
As a result of potential for neurologic occasions, together with altered psychological standing or seizures, sufferers receiving BREYANZI are in danger for creating altered or decreased consciousness or impaired coordination within the 8 weeks following BREYANZI administration. Advise sufferers to chorus from driving and interesting in hazardous occupations or actions, comparable to working heavy or doubtlessly harmful equipment, for at the least 8 weeks.

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Hostile Reactions
The most typical nonlaboratory antagonistic reactions (incidence ≥ 30%) are fever, CRS, fatigue, musculoskeletal ache, and nausea.

The most typical Grade 3-4 laboratory abnormalities (≥ 30%) embody lymphocyte depend lower, neutrophil depend lower, platelet depend lower, and hemoglobin lower.

Please see full Prescribing Info, together with Boxed WARNINGS and Medicine Information.

Bristol Myers Squibb: Making a Higher Future for Individuals with Most cancers

Bristol Myers Squibb is impressed by a single imaginative and prescient — remodeling sufferers’ lives by way of science. The objective of the corporate’s most cancers analysis is to ship medicines that provide every affected person a greater, more healthy life and to make treatment a chance. Constructing on a legacy throughout a broad vary of cancers which have modified survival expectations for a lot of, Bristol Myers Squibb researchers are exploring new frontiers in personalised medication and, by way of progressive digital platforms, are turning information into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated analysis platforms uniquely place the corporate to strategy most cancers from each angle.

Most cancers can have a relentless grasp on many components of a affected person’s life, and Bristol Myers Squibb is dedicated to taking actions to handle all features of care, from prognosis to survivorship. As a pacesetter in most cancers care, Bristol Myers Squibb is working to empower all folks with most cancers to have a greater future. Study extra concerning the science behind cell remedy and ongoing analysis at Bristol Myers Squibb right here.

About Bristol Myers Squibb
Bristol Myers Squibb is a world biopharmaceutical firm whose mission is to find, develop and ship progressive medicines that assist sufferers prevail over severe ailments. For extra details about Bristol Myers Squibb, go to us at BMS.com or observe us on LinkedIn, Twitter, YouTube, Fb and Instagram.

Cautionary Assertion Concerning Ahead-Wanting Statements
This press launch comprises “forward-looking statements” throughout the that means of the Non-public Securities Litigation Reform Act of 1995 relating to, amongst different issues, the analysis, improvement and commercialization of pharmaceutical merchandise. All statements that aren’t statements of historic info are, or could also be deemed to be, forward-looking statements. Such forward-looking statements are based mostly on present expectations and projections about our future monetary outcomes, targets, plans and aims and contain inherent dangers, assumptions and uncertainties, together with inner or exterior elements that would delay, divert or change any of them within the subsequent a number of years, which are tough to foretell, could also be past our management and will trigger our future monetary outcomes, targets, plans and aims to vary materially from these expressed in, or implied by, the statements. These dangers, assumptions, uncertainties and different elements embody, amongst others, that future examine outcomes is probably not in keeping with the outcomes thus far, that Breyanzi (lisocabtagene maraleucel) could not obtain regulatory approval for the extra indication described on this launch within the presently anticipated timeline or in any respect, that any advertising approvals, if granted, could have vital limitations on their use, and, if authorized, whether or not such product candidate for such extra indication described on this launch can be commercially profitable. No forward-looking assertion could be assured. Ahead-looking statements on this press launch must be evaluated along with the numerous dangers and uncertainties that have an effect on Bristol Myers Squibb’s enterprise and market, significantly these recognized within the cautionary assertion and threat elements dialogue in Bristol Myers Squibb’s Annual Report on Kind 10-Okay for the yr ended December 31, 2022, as up to date by our subsequent Quarterly Stories on Kind 10-Q, Present Stories on Kind 8-Okay and different filings with the Securities and Trade Fee. The forward-looking statements included on this doc are made solely as of the date of this doc and besides as in any other case required by relevant legislation, Bristol Myers Squibb undertakes no obligation to publicly replace or revise any forward-looking assertion, whether or not because of new info, future occasions, modified circumstances or in any other case.

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