Written in Blood
LYRIC Study : In the Age of Immunomodulatory Therapy , Do We Need New Lymphoma Response Criteria ?
Since the first internationally accepted response criteria , the Lugano Classification Response Criteria , were published in 1999 , advances in immunomodulatory therapies have resulted in the need for revised criteria for staging and response . To redefine response outcomes with use of immunomodulatory drugs , Bruce D . Cheson , MD , from the Georgetown University Hospital Lombardi Comprehensive Cancer Center in Washington , DC , and authors coined the term “ Indeterminate Response ( IR ),” which they reviewed in an article published in Blood . 1
“ We are encountering an increasing number of drugs , other than traditional cytotoxic chemotherapy , with which response assessment may be complicated by the development of a flare reaction , also called ‘ pseudoprogression ’,” Dr . Cheson told ASH Clinical News . “ This follows several potential patterns : an increase in the size of lesions , the development of new lesions despite regression of the initial lesions , or increased F-fluorodeoxyglucose ( FDG ) -avidity despite no change in lesion size . Unless this phenomenon is recognized , patients may be taken off a drug that is actually effective .”
The proposed provisional modification , the LYmphoma Response to Immunomodulatory Therapy Criteria ( LYRIC ), introduced IR as a more flexible classification than those provided in the Lugano Classification . “ The term ‘ IR ’ does not make a direct reference to the underlying mechanism , recognizing that a delayed response and an immune-mediated flare can both occur in the early treatment period and may be difficult to distinguish from progression by physical exam or imaging alone ,” Dr . Cheson and authors wrote . “ Moreover , the term provides the flexibility to allow patients to continue treatment past IR in some circumstances with a mandatory subsequent evaluation within 12 weeks to confirm or refute true progressive disease .”
IR is defined as one or more of the following :
• an increase in overall tumor burden of ≥50 % of up to six measurable lesions in the first 12 weeks of therapy , without clinical deterioration
• appearance of new lesions or growth of one or more existing lesions ≥50 % at any time during treatment occurring in the context of lack of overall progression of overall tumor burden
• an increase in FDG uptake of one or more lesions without a concomitant increase in lesion size or number
If patients are categorized as IR , a mandatory repeat imaging is required after 12 weeks and response should be re-evaluated with the following considerations :
• The comparison should be between the first IR and the current overall tumor burden , with an increase of ≥10 % constituting progressive disease . An increase of ≥5 mm of at least one lesion for lesions ≤2 cm and 10 mm for lesions > 2 cm should also be considered .
• The new or growing lesions should be added to the target lesions , up to a total of more than six lesions .
NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy .
IMPORTANT SAFETY INFORMATION FOR NINLARO
WARNINGS AND PRECAUTIONS
• Thrombocytopenia has been reported with NINLARO . During treatment , monitor platelet counts at least monthly , and consider more frequent monitoring during the first three cycles . Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines . Adjust dosing as needed . Platelet nadirs occurred between Days 14-21 of each 28-day cycle and recovered to baseline by the start of the next cycle .
• Gastrointestinal Toxicities , including diarrhea , constipation , nausea and vomiting , were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications , and supportive care . Diarrhea resulted in the discontinuation of one or more of the three drugs in 1 % of patients in the NINLARO regimen and < 1 % of patients in the placebo regimen . Adjust dosing for severe symptoms .
• Since inflammatory response may result in an increase in the standardized uptake value of a lesion , the patient will not be considered to have progressive disease unless there is evidence of progressive disease by an increase in lesion size or the development of a new lesion .
“ We propose that the modified response criteria be incorporated as secondary endpoints in upcoming clinical trials of
EXTEND EFFICACY .
EXTEND THE POSSIBILITIES .
• Peripheral Neuropathy ( predominantly sensory ) was reported with NINLARO . The most commonly reported reaction was peripheral sensory neuropathy ( 19 % and 14 % in the NINLARO and placebo regimens , respectively ). Peripheral motor neuropathy was not commonly reported in either regimen (< 1 %). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1 % of patients in both regimens . Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed .
• Peripheral Edema was reported with NINLARO . Monitor for fluid retention . Investigate for underlying causes when appropriate and provide supportive care as necessary . Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms .
• Cutaneous Reactions : Rash , most commonly maculopapular and macular rash , was reported with NINLARO . Rash resulted in discontinuation of one or more of the three drugs in < 1 % of patients in both regimens . Manage rash with supportive care or with dose modification .
• Hepatotoxicity has been reported with NINLARO . Drug-induced liver injury , hepatocellular injury , hepatic
18 ASH Clinical News
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