How I Treat In Brief
In “ How I Treat In Brief ,” we summarize recent “ How I Treat ” review articles , offering condensed versions of the diagnostic and therapeutic advice presented by experts in the field published in Blood . Here , Lapo Alinari , MD , PhD , and Kristie A . Blum , MD , discuss treatment options for patients with classical Hodgkin lymphoma ( cHL ) whose disease has not responded to frontline chemotherapy and relapsed following autologous hematopoietic cell transplantation ( AHCT ).
This material was repurposed from “ How I Treat Relapsed Classical Hodgkin Lymphoma After Autologous Stem Cell Transplant ,” published in the January 21 , 2016 , edition of Blood .
Post-Transplant , Relapsed Classical Hodgkin Lymphoma
lthough cHL is highly curable with chemotherapy , up to 50 percent of patients have primary refractory disease , relapse after first-line chemotherapy , or relapse after high-dose therapy and AHCT . AHCT for patients with relapsed / refractory disease after frontline chemotherapy leads to five-year PFS rates of 40 to 60 percent , with a median overall survival ( OS ) of one to two years . Novel therapies to treat this subset of patients , as well as the availability of allogeneic HCT ( alloHCT ) for select patients , may help improve OS .
We advocate for a tailored therapeutic approach for patients with relapsed cHL , guided by patient-specific characteristics including age , comorbidities , sites of disease , previous chemosensitivity , and goals of treatment ( longterm disease control or proceeding to alloHCT ; see FIGURE ).
First Choice for cHL : Brentuximab Vedotin
Brentuximab vedotin , an anti-CD30 monoclonal antibody conjugate , was approved by the U . S . Food and Drug Administration ( FDA ) in 2011 for cHL that has relapsed after AHCT or two prior chemotherapy regimens . In a pivotal phase II study , 75 percent of patients responded to brentuximab vedotin ; of the 34 percent who achieved complete remission ( CR ), a subset ( younger patients with relapsed , early-stage disease ) experienced prolonged disease control .
Based on the exceptionally high overall response rate ( ORR ) with brentuximab vedotin in patients with relapsed or refractory cHL after AHCT , it is our firstline recommendation . This should be offered at the time of relapse , as patients achieving a CR may have a prolonged remission duration exceeding four years .
For patients with primary refractory disease , relapse within 12 months , or extranodal disease , treatment with brentuximab vedotin consolidation following AHCT should be offered starting one to two months post-transplant .
Treatment Following Brentuximab Vedotin
Subsequent treatment options include :
• observation for asymptomatic patients with a low disease burden
• involved-field radiation therapy ( IFRT ) for patients with limited disease in fields amenable to radiation
• single-agent chemotherapy or combination chemotherapy
• checkpoint inhibitors and immunomodulatory therapy
• clinical trials with novel agents
FIGURE . Suggested Treatment Algorithm for Patients With cHL Who Relapse After AHCT
Treatment decisions for patients with cHL that relapses after AHCT and who have received brentuximab vedotin should be based on the extent and location of disease , symptoms , patient comorbidities and age , patient preference , and the long-term goals of therapy ( i . e ., prolonged disease control vs . achievement of best response prior to alloHCT ).
Observation In those who achieve a CR with brentuximab vedotin , particularly younger patients with low-risk early-stage disease , it is reasonable to observe them without additional consolidative therapy or alloHCT , in light of longterm response data .
Involved-Field Radiation Therapy IFRT may lead to prolonged remissions and delay the need for palliative chemotherapy in patients with cHL who relapse after AHCT with localized disease and , in certain patients , may delay the use of chemotherapy and lead to durable remissions . In addition , it is important to note that a small number of patients with cHL who relapse after AHCT could potentially be cured with radiotherapy . The patients who appear to potentially benefit the most from this approach are those with positron emission tomography and computed tomography documented stage I or II disease at relapse , disease confined to previously unirradiated lymph nodes , and those without B symptoms .
Single-Agent and Combination Chemotherapy There are a variety of single-agent chemotherapy regimens available for patients with relapsed cHL , including :
AlloHCT AlloHCT
• gemcitabine
AlloHCT
• etoposide
Brentuximab or brentuximab-containing clinical trial
cHL = classical Hodgkin lymphoma AHCT = autologous hematopoietic cell transplantation AlloHCT = allogeneic hematopoietic cell transplantation XRT = radiation therapy
Nivolumab , pembrolizumab , or checkpoint inhibitorcontaining clinical trial
• vinorelbine
• vinblastine
• liposomal doxorubicin
• bendamustine
Many of these agents can be continued until best response or disease progression . Response rates to these therapies range from 30 to 72 percent .
For those with extranodal or organ involvement who are symptomatic or need an optimal response prior to alloHCT , many interchangeable combination regimens can be considered ( see TABLE ), which have been largely used as salvage treatment options in the pre-AHCT setting , leading to ORRs of 69 to 100 percent .
Limited data on the use of these combinations are available in the post-AHCT setting ; however , when used post-AHCT , most of these regimens are associated with higher rates of grade 3-4 myelosuppression than observed
64 ASH Clinical News February 2018