we report a 53-year - old man who was diagnosed with chronic lymphocytic leukemia ( cll ) in 2012 , after presenting to the emergency room with a white blood cell count of 23,200 with 78% lymphocytes and enlarged cervical nodes . a bone marrow biopsy was performed ; pathologic findings were consistent with cll without cytogenetic or fish abnormalities . however , a ct scan 3  months after treatment completion showed extensive cervical , axillary , mediastinal , and retroperitoneal adenopathy . he was then started on rituximab and bendamustine , but treatment was discontinued early because of rash . figure1 , panel a , shows the pet scan performed prior to starting third line therapy with single agent ofatumumab . due to concern about possible transformation , he was then started on a dose - adjusted rituximab , etoposide , prednisone , vincristine , cyclophosphamide , and doxorubicin , ( r - epoch ) regimen , with persistent disease . biopsy of a left axillary lymph axillary node confirmed transformation to diffuse large b cell lymphoma , nongerminal center origin . he was then treated with rituximab , ifosfamide , carboplatin , and etoposide ( r - ice ) and rituximab , dexamethasone , high dose cytarabine , and carboplatin ( r - dhac ) and high - dose cyclophosphamide , with suboptimal response ( fig.1 , panel b ) . diagnosis and treatment timeline cll , chronic lymphocytic leukemia ; fcr , fludarabine , cyclophosphamide , and rituximab . pet scan with arrows pointing to areas of maximum standardized uptake value ( suv ) . the patient then began taking a combination of rituximab ( 375  mg / m weekly ) and ibrutinib ( 420  mg daily ) . within one month of starting therapy , no lymph nodes were clinically palpable and pet scan showed significant response in the majority of involved lymph nodes ( fig.1 , panel c ) . it is considered to have a worse prognosis than either cll or de novo diffuse large b cell lymphoma . about 1% of cll cases annually transform to a more aggressive lymphoma . while most transformations are to diffuse large b cell lymphoma , transformations to other disorders , such as hodgkin lymphoma , risk factors for transformation include advanced rai stage at diagnosis and lymph nodes > 3  cm on physical examination 2 . since richter syndrome may not involve all lymph nodes simultaneously , it is important to obtain a pet scan to guide biopsy of suspected areas prior to initiation of therapy 2 . a standard uptake value ( suv ) max of 5 is sensitive and specific for diagnosing richter syndrome ; however an suv max of 10 is independently associated with a shorter overall survival 3 . the prognosis for patients with richter syndrome is poor , and hematopoietic transplant is recommended in patients who do respond to therapy . our patient had a richter score of 1 at diagnosis which correlates with a median survival of 1.12  years 4 . in addition , he had no response to multiple regimens , and the combination of ibrutinib and rituximab was initially given with palliative intent . this kinase is located downstream from the b cell receptor and is necessary for the activation of pathways linked to cll cell survival 5 . several recently published studies reported better progression - free and overall survival and response rates in patients with cll without evidence of transformation 6,7 . an unpublished phase 1b / ii trial was conducted to study the combination of ofatumumab and ibrutinib reported a partial response in 2 of 3 study participants with richter syndrome 8 . further , ibrutinib has shown activity combined with rituximab and bendamustine in diffuse large b cell lymphoma 9 . we speculate ibrutinib may inhibit downstream signals important for malignant b cell proliferation ; however the effect was not durable possibly due to the development of acquired resistance to ibrutinib 10 . importantly , our patient did not have lymphocytosis during therapy and previous data has suggested that prolonged lymphocytosis may decrease risk of relapse 10 . to our knowledge , no previous reports have described using the combination of ibrutinib and rituximab in a heavily pretreated patient with richter syndrome . in this patient , lymphadenopathy rapidly diminished after 4  weeks of a combined regimen of rituximab and ibrutinib . this case highlights the importance of further investigation of combined ibrutinib and rituximab for patients with richter syndrome .
key clinical messagewe report a 53-year - old man diagnosed with richter syndrome . 
 he was heavily pretreated and was refractory to prior therapy . he received rituximab and ibrutinib , and achieved a significant response after 1  month of therapy . 
 our case illustrates the importance of investigation of rituximab and ibrutinib in richter s syndrome .