Bortezomib, Lenalidomide and Dexamethasone Combination Induced Complete Remission in Relapsed/Refractory Plasmablastic Lymphoma: Case Report of a Potential Novel Treatment Approach

Round 1

Reviewer 1 Report

The case report of a  patient with relapsed palsmablastic lymphoma  responding to a myleoma like association of  bortezomib , lenalidomide and dexametasone is reported 

The paper i  well written and the description  of  the disease and the activity of the agents is focused 

Some comments 

The description of the first line treatment and its complication can be shortened 

How was the length of lenalidomide maintence established ?

The discussion is compelte as well as the bibiographic references 

Author Response

1. As per the suggestion, the description of the first-line treatment and its complications has been shortened and updated in the manuscript. 
2.  The length of Lenalidomide maintenance was extrapolated from our experience with myeloma-related regimens.  Taking into account the risk of secondary malignancies we did not continue prolonged administration of lenalidomide and restricted it to 18 months. 

Reviewer 2 Report

This is an interesting case. I found some minor problems:

1) Page 5 line 204-207: The numbers do not fit and should be corrected.

2) page 5 line 200: Substitute the word "was" by "with".

3) page 6 line 221: correct as follows: series of 16 patients.

4) page 7 line 259: correct: PBL.

5) page 9: correct: Brentuximab.

Author Response

As suggested by reviewer 2 , I have done the changes listed 1 to 5.

Reviewer 3 Report

This is an interesting case report to demonstrate of the efficacy of  bortezomib-based plasma cell targeted regimen (combining bortezomib,lenalidomide and dexamethasone) for a relapsed plasmablastic lymphoma (PBL) which was refractory to conventional chemotherapy in an HIV-negative patient. 

Extramedullary plasmacytomas are often localized, clinically indolent neoplasms, and affected patients usually respond to radiation therapy or limited cycles of chemotherapy. In contrast, plasmablastic lymphomas are clinically aggressive neoplasms composed of immunoblastic or plasmablastic cells and associated with more mature plasma cells in some cases. Patients with plasmablastic lymphoma usually have a poor prognosis despite aggressive chemotherapy. Evidence of Epstein-Barr virus (EBV) infection is uncommon in plasmacytoma, but common in plasmablastic lymphoma, and is therefore helpful in differential diagnosis.

The finding provides novel therapeutic approaches on how to treat PBL.  The manuscript can be improved if the authors revise in the following aspects. 

1. Please provide the classical high-resolution pathology pictures of the PBL diagnosis including the EBV-ish, p53 result as well as the biomarkers including c-MCY and CD38 express for potential targeted therapy with Daratumumab. 

2.  What is the cytogenetics or FISH result of the abnormality?

3.  In the literature, some of the plasmacytoma can be EBV+ in an immunocompetent patient.  EBV-positive plasmacytoma can cause a diagnostic dilemma as it may morphologically and phenotypically overlap with a clinically aggressive plasmablastic lymphoma (PBL).   Please discuss the differential diagnosis and update of the literature (Sanam Loghavi. Epstein-Barr virus-positive plasmacytoma in immunocompetent patientsHistopathology. 2015 Aug;67(2):225-34.) 

Author Response

1. Pictures added in the manuscript - Figure 1
2. FISH analyses were performed on the paraffin block of this sinonasal mass specimen. c-MYC gene rearrangement is negative. Multiple myeloma FISH panels (1p32.3/1q21 CDKN2C/CKS1B, del(13q)/13q14/13q34 and del(17p)TP53) are negative for abnormalities. Same is added in the manuscript. 
3. Reference added and discussed :  

   Morphologically, the tumor cells  are large in size and show conspicuous nucleoli, associated with increased mitotic figures and apoptotic bodies. In conjunction with the location of this mass lesion (sinonasal cavity), patient’s prior clinical history (eosinophilic granulomatosis with polyagngitis, associated with chronic steroid use) that indicates iatrogenic immunosuppression status in this patient, and diffusely strong EBV positivity in the tumor cells, the overall findings are most compatible with a diagnosis of plasmablastic lymphoma.

    In contrast, EBV positive plasmacytoma usually shows obvious mature plasma cell morphology and is presented by immunocompetent patients.

Round 2

Reviewer 3 Report

The paper was revised appropriately,