U.S. FDA Approves Pfizer’s ADCETRIS® Combination Regimen for the treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Pfizer (NYSE: PFE) has received FDA approval for ADCETRIS® combination therapy for treating relapsed/refractory large B-cell lymphoma (LBCL). The approval is based on the Phase 3 ECHELON-3 trial results, which showed the ADCETRIS regimen reduced death risk by 37% compared to standard treatment.
The therapy is specifically approved for adult patients with LBCL who have undergone two or more lines of systemic therapy and are not eligible for stem cell transplantation or CAR-T therapy. This marks ADCETRIS's eighth FDA-approved indication.
The ECHELON-3 study demonstrated significant improvement in overall survival, with benefits consistent across CD30 expression levels. More than 3,500 patients annually in the U.S. experience treatment failure after two prior therapy lines for this aggressive form of non-Hodgkin lymphoma.
Pfizer (NYSE: PFE) ha ricevuto l'approvazione della FDA per la terapia combinata con ADCETRIS® per il trattamento del linfoma diffuso a grandi cellule B (LBCL) in recidiva/refrattario. L'approvazione si basa sui risultati dello studio di Fase 3 ECHELON-3, che ha dimostrato che il regime ADCETRIS ha ridotto il rischio di morte del 37% rispetto al trattamento standard.
La terapia è specificamente approvata per pazienti adulti con LBCL che hanno ricevuto due o più linee di terapia sistemica e non sono idonei al trapianto di cellule staminali o alla terapia CAR-T. Questo segna l'ottava indicazione approvata dalla FDA per ADCETRIS.
Lo studio ECHELON-3 ha dimostrato un miglioramento significativo nella sopravvivenza complessiva, con benefici coerenti tra i livelli di espressione di CD30. Più di 3.500 pazienti all'anno negli Stati Uniti sperimentano il fallimento del trattamento dopo due linee di terapia precedenti per questa forma aggressiva di linfoma non-Hodgkin.
Pfizer (NYSE: PFE) ha recibido la aprobación de la FDA para la terapia combinada con ADCETRIS® para tratar el linfoma de células B grandes (LBCL) en recaída/refractario. La aprobación se basa en los resultados del ensayo de Fase 3 ECHELON-3, que mostró que el régimen de ADCETRIS redujo el riesgo de muerte en un 37% en comparación con el tratamiento estándar.
La terapia está específicamente aprobada para pacientes adultos con LBCL que han recibido dos o más líneas de terapia sistémica y no son elegibles para trasplante de células madre o terapia CAR-T. Esto marca la octava indicación aprobada por la FDA para ADCETRIS.
El estudio ECHELON-3 demostró una mejora significativa en la supervivencia general, con beneficios consistentes en todos los niveles de expresión de CD30. Más de 3.500 pacientes anualmente en EE. UU. experimentan fallo en el tratamiento después de dos líneas de terapia previas para esta forma agresiva de linfoma no Hodgkin.
화이자 (NYSE: PFE)는 재발/불응성 대형 B 세포 림프종 (LBCL) 치료를 위한 ADCETRIS® 병용 요법에 대해 FDA 승인을 받았습니다. 이 승인은 ADCETRIS 요법이 표준 치료에 비해 사망 위험을 37% 감소시켰다는 3상 ECHELON-3 시험 결과에 기반합니다.
이 요법은 두 가지 이상의 전신 요법을 받았고 줄기세포 이식이나 CAR-T 요법에 적합하지 않은 LBCL 성인 환자에게 특별히 승인되었습니다. 이는 ADCETRIS의 FDA 승인 적응증이 여덟 번째입니다.
ECHELON-3 연구는 CD30 발현 수준에 관계없이 전반적인 생존율의 유의미한 개선을 보여주었습니다. 매년 미국에서 3,500명 이상의 환자가 이 공격적인 비호지킨 림프종의 두 가지 이전 치료 후 치료 실패를 경험합니다.
Pfizer (NYSE: PFE) a reçu l'approbation de la FDA pour la thérapie combinée avec ADCETRIS® pour traiter le lymphome à grandes cellules B (LBCL) en rechute/réfractaire. L'approbation est basée sur les résultats de l'essai de phase 3 ECHELON-3, qui a montré que le régime ADCETRIS réduisait le risque de décès de 37% par rapport au traitement standard.
La thérapie est spécifiquement approuvée pour les patients adultes atteints de LBCL qui ont reçu deux lignes de thérapie systémique ou plus et qui ne sont pas éligibles pour une transplantation de cellules souches ou une thérapie CAR-T. Cela marque la huitième indication approuvée par la FDA pour ADCETRIS.
L'étude ECHELON-3 a démontré une amélioration significative de la survie globale, avec des bénéfices cohérents à travers les niveaux d'expression de CD30. Plus de 3 500 patients chaque année aux États-Unis connaissent un échec de traitement après deux lignes de thérapie antérieures pour cette forme agressive de lymphome non hodgkinien.
Pfizer (NYSE: PFE) hat die FDA-Zulassung für die Kombinationstherapie mit ADCETRIS® zur Behandlung von rezidivierenden/refraktären großzelligen B-Zell-Lymphomen (LBCL) erhalten. Die Genehmigung basiert auf den Ergebnissen der Phase-3-Studie ECHELON-3, die zeigte, dass das ADCETRIS-Regime das Sterberisiko um 37% im Vergleich zur Standardbehandlung senkte.
Die Therapie ist speziell für erwachsene Patienten mit LBCL genehmigt, die zwei oder mehr Linien systemischer Therapie durchlaufen haben und nicht für eine Stammzelltransplantation oder CAR-T-Therapie geeignet sind. Dies ist die achte von der FDA genehmigte Indikation für ADCETRIS.
Die ECHELON-3-Studie zeigte eine signifikante Verbesserung der Gesamtüberlebensrate, wobei die Vorteile über alle CD30-Expressionsniveaus hinweg konsistent waren. Jährlich erleben mehr als 3.500 Patienten in den USA nach zwei vorherigen Therapie-Linien einen Behandlungsversagen bei dieser aggressiven Form von Non-Hodgkin-Lymphom.
- FDA approval for ADCETRIS combination therapy represents 8th approved indication
- 37% reduction in death risk compared to standard treatment
- Demonstrated statistically significant improvement in overall survival
- Efficacy shown regardless of CD30 expression levels
- Addresses large market with over 3,500 annual patients requiring third-line therapy
- Notable adverse events including Grade 3 neutropenia (43%), thrombocytopenia (25%), and anemia (22%)
- to patients ineligible for stem cell transplantation or CAR-T therapy
Insights
The FDA approval of ADCETRIS combination therapy for relapsed/refractory DLBCL represents a significant commercial opportunity for Pfizer in the lymphoma market. The demonstrated 37% reduction in mortality risk positions this therapy as a potentially dominant player in the third-line treatment landscape, particularly given its outpatient administration advantage over CAR-T therapy.
Several key factors enhance the commercial potential: First, the therapy's efficacy across CD30 expression levels expands the eligible patient population, eliminating the need for biomarker testing. Second, the outpatient administration provides a significant cost advantage over CAR-T therapy, which requires hospitalization. With approximately 3,500 annual U.S. patients requiring third-line therapy, and considering the typical pricing for novel oncology combinations, this approval could generate substantial recurring revenue.
The robust safety profile, with manageable and predictable adverse events, should support rapid adoption among physicians. The combination's effectiveness in heavily pre-treated patients, including those who received prior CAR-T therapy, positions it as both a competitive third-line option and a potential salvage therapy. This versatility, combined with ADCETRIS's established presence in the lymphoma market through its seven other indications, provides Pfizer with significant leverage in formulary negotiations and market access discussions.
This approval strengthens Pfizer's oncology portfolio at a important time, as the company seeks to offset revenue declines in other areas. The expansion into aggressive B-cell lymphomas complements Pfizer's existing presence in hematologic malignancies and could serve as a springboard for further development in earlier lines of therapy.
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Approval is based on positive data from the Phase 3 ECHELON-3 trial, which demonstrated ADCETRIS regimen reduced the risk of death by
37% , a statistically significant, clinically meaningful improvement in overall survival (OS), compared to lenalidomide and rituximab plus placebo
- ECHELON-3 is the first Phase 3 trial to demonstrate OS advantage over lenalidomide and rituximab plus placebo for patients with at least 2 prior lines of therapy with R/R diffuse large B-cell lymphoma (DLBCL)
- Milestone represents the eighth FDA-approved indication for ADCETRIS, reinforcing its use as a standard of care for certain lymphomas
“Each year, more than 3,500 patients in the
The approval is based on efficacy and safety data from the Phase 3 ECHELON-3 study, which demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with relapsed/refractory DLBCL who received ADCETRIS in combination with lenalidomide and rituximab. The study included patients who were heavily pre-treated, some of whom had received prior CAR-T therapy, and survival benefit was observed irrespective of CD30 expression.
“Patients with large B-cell lymphoma can face a challenging journey, with too many patients enduring multiple rounds of chemotherapy and even CAR-T therapy with limited success,” said principal investigator Dr. Craig Portell, Associate Professor, University of
LBCL is a type of non-Hodgkin lymphoma (NHL), that affects immune cells called B lymphocytes, a type of white blood cell crucial to the body's immune system. DLBCL is the most common, aggressive and difficult-to-treat form of the disease. More than 25,000 cases of DLBCL are diagnosed each year in
The ECHELON-3 study showed that the ADCETRIS combination reduced patients’ risk of death by
The safety profile of ADCETRIS in ECHELON-3 was consistent with its known safety profile as presented in the
Detailed data from ECHELON-3 were published in JCO Oncology Practice on January 7, 2025 and presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
About ECHELON-3
ECHELON-3 is an ongoing, randomized, double-blind, multicenter Phase 3 study evaluating ADCETRIS plus lenalidomide and rituximab versus lenalidomide and rituximab plus placebo in adult patients with relapsed/refractory or transformed DLBCL, regardless of CD30 expression, who have received two or more prior lines of therapy and are ineligible for stem cell transplant (HSCT) or CAR-T therapy. The study also includes patients with hard-to-treat subtypes with poorer outcomes including double hit/triple hit lymphoma and patients with transformed disease. Patients may be ineligible to receive either HSCT or CAR-T therapy due to co-morbidities or financial, geographic, insurance, manufacturing issues. In this global study, 230 patients were randomized across
About Large B-cell Lymphoma
LBCL accounts for about 1/3 of cases of NHL, a type of cancer that starts in the lymphocytes and affects immune cells called B lymphocytes. LBCL occurs most often in older people, with a median age of 67 at diagnosis. About 60
DLBCL is the most common and aggressive type of LBCL and is difficult to treat. More than 25,000 cases of DLBCL are diagnosed each year in
About ADCETRIS
More than 55,000 patients have been treated with ADCETRIS in the
ADCETRIS is an antibody-drug conjugate (ADC) comprised of a CD30-directed monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Pfizer's proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.
ADCETRIS is approved in eight indications in the
- Adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) NOS, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for auto-HSCT or chimeric antigen receptor (CAR) T-cell therapy, in combination with lenalidomide and a rituximab product (2025)
- Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (2018)
- Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022)
- Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015)
- Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011)
- Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018)
- Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. (2011)
- Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017)
Pfizer and Takeda jointly develop ADCETRIS. Under the terms of the collaboration agreement, Pfizer has
ADCETRIS® (brentuximab vedotin) for injection
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML, and death can occur in ADCETRIS-treated patients.
CONTRAINDICATION
Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
WARNINGS AND PRECAUTIONS
Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.
Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL or relapsed or refractory LBCL and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.
Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.
Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.
Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment.
Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.
Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
Serious dermatologic reactions: Fatal and serious cases of Stevens-
Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with pre-existing GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.
Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.
Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS.
ADVERSE REACTIONS
The most common adverse reactions (≥
The most common Grade ≥3 adverse reactions (≥
DRUG INTERACTIONS
Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during ADCETRIS treatment.
Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here. There may be a delay as the document is updated with the latest information. It will be available as soon as possible. Please check back for the updated full information shortly.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
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Disclosure Notice
The information contained in this release is as of February 12, 2025. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about Pfizer Oncology and ADCETRIS (brentuximab vedotin), including its potential benefits, an approval in the
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the
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FAQ
What was the primary outcome of Pfizer's (PFE) ECHELON-3 trial for ADCETRIS?
What patient population is eligible for PFE's newly approved ADCETRIS combination therapy?
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How many FDA-approved indications does Pfizer's (PFE) ADCETRIS now have?
