During a Targeted Oncology™ Case-Based Roundtable™ event, Craig Moskowitz, MD, discussed the use of brentuximab vedotin in patients with Hodgkin lymphoma. This is the second of 2 articles based on this event.
Craig Moskowitz, MD
Professor
Physician-in-Chief, Oncology Service Line
Don Soffer Clinical Research Center
University of Miami Sylvester Comprehensive Cancer Center
Miami, FL
[Read Part 1]
Targeted Oncology: When looking at toxicities leading to death reported in the ECHELON-1 trial (NCT01712490), how do we know that pulmonary fibrosis toxicity reported in patients receiving frontline ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for Hodgkin lymphoma isn’t related to receiving bleomycin?
CRAIG MOSKOWITZ, MD: [The toxicity] happens late. [Older physicians have seen] patients die from bleomycin. It never happens early. It's unusual to die from bleotoxicity in patients who just get ABVD unless they are older, and we don't give bleomycin to patients who are older than 60 years anymore.
But in a younger patient who dies from pulmonary toxicity who received ABVD, a lot of times they have relapsed, and they've also had radiation therapy, and maybe BCNU [carmustine] as part of an [autologous stem cell transplant], so it's hard to tease out. But older patients, in effect, there was a study [North American Intergroup E2496 Trial; NCT00003389] that…compared ABVD with Stanford V [mechlorethamine, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide and prednisone], and that was a negative study.1 In that study, the elderly cohort had an 18% death rate, and the majority was from bleomycin. So what we learned from that is that when you're older than 60 years, you probably shouldn't get bleomycin.
But in the younger patients, it's very rare. You'd have to probably have some other underlying genetic abnormality to die from bleotoxicity when you're young.
What else stands out concerning the safety and survival outcomes of the ECHELON-1 trial comparing ABVD with BV-AVD (brentuximab vedotin [Adecetris], doxorubicin, vinblastine, and dacarbazine)?
Looking at deaths on treatment in the ECHELON-1 trial, it's hard for me to understand. The most common secondary malignancy in the groups of patients with ABVD was large cell lymphoma,2 which makes me think they already had large cell lymphoma, [but] it was just misdiagnosed, so I don't think anything of [those data], other than the fact that more patients who got ABVD died from Hodgkin lymphoma [or its complications].
I don't think there's a difference in secondary malignancies. I also don't think there is much of a difference with safety. There is more pulmonary toxicity with ABVD and there's more neurotoxicity with BV-AVD, and [for physicians] who don't use a lot of BV, you need to know that if [the patient] can't button their shirt or zip their fly or write a check, you probably need to reduce the dose of brentuximab. I always ask patients, “Can you button this button on your shirt?” If you can't button this button because of neuropathy, it's always grade 2, and [BV] has to be reduced to 0.9 mg/kg. If it's worse than that, you have to drop BV.
How do these therapies impact pregnancy and fertility?
We take care of a lot of young women and a lot of young women are pregnant with Hodgkin lymphoma…. The patients are always undertreated, but there's no difference in the pregnancy rate with BV-AVD and ABVD, which is key.2
I don't necessarily know the sperm data with BV-AVD. All the men [used] a sperm bank anyway, but the female pregnancy rate [of partners of men treated for Hodgkin lymphoma] is pretty good.
What dose modifications are required for patients with peripheral neuropathy with BV?
When we see somebody with [peripheral neuropathy related to] BV-AVD, and I think our chief complaint that we get is the patients have bone pain from pegfilgrastim [Neulasta]. The patients are young, and that's their chief complaint. And then when we tell them we can change them to G-CSF [granulocyte-colony stimulating factor]. I usually give G-CSF on day 6 through 10, and if the counts are too high, we can reduce it by a day, and if it's still too high, we can give 3 doses. They don't always say yes, because they don't want to self-inject. But that's by far the biggest complaint that we have, which is much different than, for example, nivolumab [Opdivo]-AVD or pembrolizumab [Keytruda]-AVD.
What immunotherapy agents are being investigated in combination with chemotherapy for Hodgkin lymphoma?
There was a huge national study [SWOG S1826 study; NCT03907488] comparing BV-AVD versus nivolumab-AVD. That study was done, and was powered for nivolumab-AVD to be 5% better than BV-AVD. It's important to think about that in a couple of ways. First, it's a United States study, so it's mandated that the patients who get BV get growth factors.
When patients who receive BV-AVD get growth factors…it's 5% better. It's probably at 84% at 5 years. Those are probably the [most significant] data with BV-AVD.3
That means we're asking nivolumab-AVD to be at 89% for advanced stage Hodgkin lymphoma at 5 years. If it's not at 89%, it's going to be a negative study. Now, of course, there are secondary end points with toxicity and whatnot, but the primary end point is efficacy, and efficacy has to be 5% better with that program.
There are many different adverse events [AEs] between these 2 programs. BV-AVD causes neuropathy, and it causes cytopenias.4 Nivolumab-AVD causes immune-related AEs, [and] thyroid dysfunction in about 15% of patients, which I don't [worry] about so much, but it's annoying.5
Rash is not easy. Rash is a real [issue] with pembrolizumab and nivolumab when combined with chemotherapy. They also get this gastrointestinal discomfort syndrome, which is hard to explain. It's not benign, even though it's outpatient treatment, but we'll see what happens when the study is reported. [I have heard] that there will be some toxicity data that's going to be reported [later this year at the International Conference on Malignant Lymphoma] out in Lugano, [Switzerland].
This study is the [SWOG S1826 study]. We [at the University of Miami] put 18 patients on, and all our patients have done well. The first 12 patients all got BV-AVD; although it's supposed to be random. I think there is 1 patient who [responded] and that patient got BV-AVD.
Merck is doing an industry-sponsored study…comparing pembrolizumab-AVD versus ABVD, and I don't know if that's being done in the United States all that much, but it’s being done quite a bit in Europe.
The phase 2 data with pembrolizumab-AVD look quite good.6 The phase 2 data with nivolumab-AVD last had been updated in 2019.7 At that point, the results were decent. Now, we have been championed a program called pembrolizumab-GVD [gemcitabine, vinorelbine, and liposomal doxorubicin], which is a study that Alison J. Moskowitz, MD, and I wrote before I left Memorial Sloan Kettering Cancer Center, and we brought that [to the University of Miami], in patients with relapsed Hodgkin lymphoma. That's one of the best treatments we've ever given, and it's phenomenal. It has a litany of AEs, but it's outpatient and it's pretty well tolerated.8
REFERENCES
1. Advani RH, Hong F, Fisher RI, et al. Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma: a subset analysis of the North American Intergroup E2496 trial.J Clin Oncol. 2015;33(17):1936-1942. doi:10.1200/JCO.2014.57.8138
2. Ansell SM, Radford J, Connors JM, et al. Overall Survival with brentuximab vedotin in stage III or IV hodgkin's lymphoma.N Engl J Med. 2022;387(4):310-320. doi:10.1056/NEJMoa2206125
3. Straus D, Collins G, Walewski J, et al. Primary prophylaxis with G-CSF may improve outcomes in patients with newly diagnosed stage III/IV Hodgkin lymphoma treated with brentuximab vedotin plus chemotherapy.Leuk Lymphoma. 2020;61(12):2931-2938. doi:10.1080/10428194.2020.1791846
4. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV hodgkin's lymphoma. N Engl J Med. 2018;378(4):331-344. doi:10.1056/NEJMoa1708984
5. Advani RH, Moskowitz AJ, Bartlett NL, et al. Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results.Blood. 2021;138(6):427-438. doi:10.1182/blood.2020009178
6. Allen PB, Savas H, Evens AM, et al. Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma.Blood. 2021;137(10):1318-1326. doi:10.1182/blood.2020007400
7. Ramchandren R, Domingo-Domènech E, Rueda A, et al. Nivolumab for newly diagnosed advanced-stage classic hodgkin lymphoma: safety and efficacy in the phase II CheckMate 205 study.J Clin Oncol. 2019;37(23):1997-2007. doi:10.1200/JCO.19.00315
8. Moskowitz AJ, Shah G, Schöder H, et al. Phase II trial of pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin as second-line therapy for relapsed or refractory classical Hodgkin lymphoma.J Clin Oncol. 2021;39(28):3109-3117. doi:10.1200/JCO.21.01056
FAQs
What is the success rate of brentuximab vedotin? ›
The median follow-up for overall survival was 73 months. In the group receiving A+AVD , 39 patients died, for an overall survival rate of 93.9%. In the group receiving ABVD , 64 patients died, for an overall survival rate of 89.4%.
What is the response rate for brentuximab? ›The objective response rate (ORR) on this pivotal trial among patients with relapsed or refractory systemic ALCL treated with single-agent brentuximab vedotin was 86% per independent review, with 57% of patients achieving a complete response (CR).
What is the length of treatment for brentuximab? ›The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. ADCETRIS treatment should start following recovery from ASCT based on clinical judgment. These patients should receive up to 16 cycles (see section 5.1).
How long does it take for brentuximab to work? ›How long until I see results? Adcetris (brentuximab vedotin) is a medicine you typically receive long-term. It will start working right after you receive it, but you will not notice changes right away.
What is the final concentration of brentuximab? ›a minimum volume of 100 mL of 0.9% Sodium Chloride Injection, 5% Dextrose Injection or Lactated Ringer's Injection to achieve a final concentration of 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin.
How much is brentuximab in USA? ›Adcetris (brentuximab) is a member of the CD30 monoclonal antibodies drug class and is commonly used for Hodgkin's Lymphoma, Lymphoma, and Mycosis Fungoides. The cost for Adcetris intravenous powder for injection 50 mg is around $11,034 for a supply of 1 powder for injection, depending on the pharmacy you visit.
What are the benefits of brentuximab? ›Brentuximab is used to treat certain types of cancers (Hodgkin's lymphoma, systemic anaplastic large cell lymphoma, peripheral T-cell lymphoma, primary cutaneous anaplastic large cell lymphoma, CD30-expressing mycosis fungoides). It works by slowing or stopping the growth of cancer cells.
What is progression free survival for Adcetris? ›The data demonstrated that the estimated five-year overall survival (OS) rate among ADCETRIS-treated patients was 41 percent (95% CI: 31%, 51%); median OS was 40.5 months (95% CI: 28.7, 61.9 [range 1.8 to 72.9+]) and median progression-free survival (PFS) was 9.3 months (95% CI: 7.1 to 12.2 months).
Do you lose your hair with brentuximab? ›Hair loss may happen suddenly or gradually. If you lose hair, you may lose it from your head, face, armpits, pubic area, chest, and/or legs. You may also notice your hair getting thin. Note: Each of the side effects above was reported in 20% or greater of patients treated with brentuximab vedotin.
What are the risks of brentuximab vedotin? ›Receiving brentuximab vedotin injection may increase the risk that you will develop progressive multifocal leukoencephalopathy (PML; a rare infection of the brain that cannot be treated, prevented, or cured and that usually causes death or severe disability).
What is the target of brentuximab? ›
Brentuximab targets a protein called CD30 that is found on Hodgkin lymphoma and anaplastic large cell lymphoma cells. Brentuximab sticks to the CD30 protein and delivers a drug to the cell. The drug then kills the cell.
What is the target of brentuximab vedotin? ›Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a toxic agent, called vedotin. Brentuximab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD30 receptors, and delivers vedotin to kill them.
What are the symptoms of a reaction to brentuximab? ›The reactions most common with brentuximab vedotin are anaphylactoid, including chills, nausea, dyspnea, pruritus, pyrexia, and cough.
How long does it take to fight lymphoma? ›A short course of treatment usually takes about 6 to 12 weeks. Or you might have a longer course of chemotherapy and a targeted drug, without radiotherapy. Whether you have radiotherapy depends on factors such as where the lymphoma is in the body and how fit you are.
How long do side effects of brentuximab last? ›You may have nausea, vomiting, and/or loss of appetite. Nausea and vomiting may begin soon after the drug is given and may last more than 24 hours. You may be given medicine to help with this.
What is the overall survival summary with brentuximab vedotin in stage 3 or 4 Hodgkin's lymphoma? ›The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86).
What is the half life of brentuximab vedotin? ›Monomethyl auristatin E is eliminated by the feces (with 72% unchanged) and urine. The terminal half-life is 4-6 days. Monomethyl auristatin E is cleared by the liver but not quantitative studies have been performed. The most severe toxic reaction seen in patients is progressive multifocal leukoencephalopathy.
What are the results of brentuximab clinical trial? ›Brentuximab vedotin plus AVD (A+AVD) had an acceptable side-effect profile and resulted in complete response in 24 of 25 patients (96%). Long-term follow-up showed a 5-year failure-free survival rate of 92% and an overall survival rate of 100% with A+AVD.
How much does lymphoma treatment cost in USA? ›For lymphoma patients without health insurance and who must self-pay for their care, the cost of treatment can be as high as $200,000 or more the first year. Even for patients with health insurance, the out-of-pocket expenses for care can be staggering.
When was brentuximab approved? ›In 2018, FDA approved brentuximab vedotin as an initial, or first-line, treatment for adults with advanced Hodgkin lymphoma.
Is brentuximab hazardous? ›
Non-infectious pulmonary toxicity, including cough, dyspnea, and interstitial infiltration and/or inflammation on imaging has been reported with single-agent brentuximab vedotin and may be fatal.
Who invented brentuximab? ›Brentuximab vedotin, developed by Seattle Genetics, Inc.
How do you adjust brentuximab for liver? ›Liver Dose Adjustments
If the recommended dose is 1.8 mg/kg (maximum 180 mg) IV over 30 minutes every 3 weeks, reduce the dose to 1.2 mg/kg (maximum 120 mg) IV over 30 minutes every 3 weeks; the dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg.
Brentuximab vedotin is an antibody that targets Hodgkin lymphoma cells. Once it binds to the lymphoma cell surface, it then enters the inside of the cancer cell. Once inside the cell, the antibody releases a drug called MMAE, which stops the cell from growing and dividing.
What is the 30 day mortality after systemic anticancer treatment? ›Overall mortality within 30 days after the start of systemic treatment was 6.2%. Only 11 (0.04%) patients died on the first day; 313 (1.2%) during the first week.
What is metastasis free survival time? ›The length of time from the start of treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body. In a clinical trial, measuring the metastasis-free survival is one way to see how well a new treatment works. Also called MFS.
How much does Adcetris cost? ›Adcetris May Cost $4,500 Per Vial, Or Over $100,000 For A Course Of Lymphoma Treatment. Adcetris (brentuximab vedotin), recently FDA approved for Hodgkin lymphoma and systemic anaplastic large cell lymphoma, may cost over $100,000 for a course of treatment, or $4,500 per vial.
What is another name for brentuximab? ›Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma.
Does brentuximab vedotin cause neuropathy? ›Background: Brentuximab vedotin (BV) is an immunoconjugate used in Hodgkin lymphoma (HL) and other CD30+ lymphomas. The dose-limiting adverse effect is peripheral neuropathy (BIPN).
Is brentuximab an immunotherapy? ›In recent years, significant advances have been made with the introduction of targeted immunotherapy such as brentuximab vedotin (BV) and nivolumab (NV).
What is the generic name for brentuximab? ›
Brentuximab vedotin is the generic name for the trade name drug Adcetris. In some cases, health care professionals may use the trade name, Adcetris, when referring to the generic drug name, brentuximab vedotin.
What is brentuximab made of? ›Brentuximab vedotin is generated by conjugating the mouse-human chimeric IgG1 anti-CD30 mAb (cAC10; SGN-30), to the synthetic dolastatin 10 analog monomethylauristatin A (MMAE), via a protease-sensitive dipeptide linker. Each mAb molecule carries an average of 4 MMAE groups.
What is targeted chemotherapy for Hodgkin's lymphoma? ›When you might have targeted drug treatments. Monoclonal antibodies (MABs) are the most common type of targeted drug used for Hodgkin lymphoma. Brentuximab and rituximab are a type of monoclonal antibody. They target specific proteins on lymphoma cells and help the immune system to pick out these cells and kill them.
What kind of drug is brentuximab vedotin? ›Brentuximab vedotin contains a monoclonal antibody that binds to a protein called CD30, which is found on some lymphoma cells. It also contains an anticancer drug, which may help kill cancer cells. Brentuximab vedotin is a type of antibody-drug conjugate.
Can Hodgkin's lymphoma be completely cured? ›Overall, treatment for Hodgkin lymphoma is highly effective and most people with the condition are eventually cured.
How long does it take to get rid of Hodgkin's lymphoma? ›Chemotherapy is given as a combination of drugs, in several cycles (or courses) of treatment with a rest period of a few weeks in between each cycle. A typical chemotherapy regime for Hodgkin lymphoma might involve around six cycles of a combination of drugs, given over a period of six months.
Can lymphoma be 100% cured? ›Lymphoma is often curable, especially in its initial stages.
What are the precautions for brentuximab? ›Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are receiving this medicine. Check with your doctor if you have a fever, chills, sore throat, or painful urination. These could be symptoms of an infection.
Is breathing a side effect of brentuximab? ›This medicine may cause an infusion reaction, which can be life-threatening and requires immediate medical attention. Tell your doctor or nurse right away if you have a fever, chills, trouble breathing, lightheadedness, fainting, or chest pain within a few hours after you receive it.
What is the success rate of ADCETRIS? ›The data demonstrated that the estimated five-year overall survival (OS) rate among ADCETRIS-treated patients was 41 percent (95% CI: 31%, 51%); median OS was 40.5 months (95% CI: 28.7, 61.9 [range 1.8 to 72.9+]) and median progression-free survival (PFS) was 9.3 months (95% CI: 7.1 to 12.2 months).
What is the survival rate for refractory Hodgkin's lymphoma? ›
Overall survival is approximately 80% to 90%. A subset of these patients has refractory disease or experience disease relapse. Conventional salvage therapies and autologous stem-cell transplantation is usually considered the standard of care for these patients.
Which B-cell lymphoma has the best prognosis? ›Of the 2 most common types of B-cell lymphoma, follicular lymphoma generally has a better prognosis than diffuse large B-cell lymphoma (DLBCL). Anaplastic large cell lymphoma and cutaneous T-cell lymphoma are 2 subtypes of T-cell lymphoma that have a fairly good prognosis.
How does brentuximab treat Hodgkin's lymphoma? ›Brentuximab targets a protein called CD30 that is found on Hodgkin lymphoma and anaplastic large cell lymphoma cells. Brentuximab sticks to the CD30 protein and delivers a drug to the cell. The drug then kills the cell.
What is the most survivable lymphoma? ›Follicular lymphoma
almost 90 in 100 people (almost 90%) survive their cancer for 5 years or more after diagnosis.
The goal of Hodgkin lymphoma treatment is to cure the disease. More than 80 percent of all patients diagnosed with Hodgkin lymphoma can be cured by current treatment approaches. The cure rate is higher, approaching 90 percent, in younger patients and those with early-stage favorable disease.
Can you live 20 years with Hodgkin lymphoma? ›90 out of 100 people (90%) will survive their Hodgkin lymphoma for 5 years or more after diagnosis.
What is the most aggressive B-cell lymphoma? ›Less common forms of B-cell lymphoma include: Burkitt lymphoma: Considered the most aggressive form of lymphoma, this disease is one of the fastest growing of all cancers.
What is the 10 year survival rate for B-cell lymphoma? ›Overall survival
OS according to IPI and R-IPI category is shown in Fig. 1; OS rates are shown in Table V. Among patients classified as having an IPI 'low risk', 80% were alive at 10 years; the 10-year OS rates in the 'low-intermediate', 'high-intermediate', and 'high-risk' groups were 60, 43, and 30%, respectively.
Hodgkin lymphoma is considered one of the most treatable cancers, with more than 90 percent of patients surviving more than five years. Most patients with Hodgkin lymphoma live long and healthy lives following successful treatment.
What is an adverse reaction to brentuximab? ›Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are receiving this medicine. Check with your doctor if you have a fever, chills, sore throat, or painful urination. These could be symptoms of an infection.