I have a patient whith PMLBCL, who progressed under DA-EPOCH-Rx6 and R-ESHAPx2 and developed CNS sec. lymphoma. Can HD Mtx HD Ara-Cx4+WBRT do anything or is it a old story for this type of lymphoma if it is resistant nothing will help. We have a plan to do auto-SCT if she responds well to H-CVAD, but is there any chance for cure? Do anyone suggest some other approach?
HDMtx would be treatment of choice. Radrx would need to treat entire CNS as usual have meningeal invasion with positive CSF. Intrathecal Mtx and ARA-C may also help in addition to HDMtx.
Agree with high dose methotrexate. Don't know how much intrathecal would add to the treatment when the patient is receiving high dose MTX.. With all the treatment, the patient has received so far, I doubt, that stem cells can be harvested for an auto-SCT. Even so, we would suggest allo-SCT in this patient who has relapsed twice. CD30 positive Non-hodgkin lymphoma can be offered Brentuximab Vedotin, but this was found ineffective in PMLBCL by Italian group (Blood 2017). Pembrolizumab was recently approved by FDA for relapsed, refractory PMLBCL, though we doubt that there would be a chance of cure short of ASCT.
Thank you for your answer-
No IT therapy is recommended during HD MTX because it is overmuch. HD MTX is enough to penetrate CSF.
By our Health Found we are limited, Adcetris and Keytruda are not approved for relapsing PMLBCL. However, the patient died, during d2 of HD MTX HD Ara C. This was unfortunatelly expected scenario-It is well known fact when PMLBC is resistant nothing can help. Theorethically Ruxolitinib as TKI can be active in this lymphoma because JAK2/STAT5 pathway is affected, but it is only hypothesis.
I would agree that a regimen such as HD-MTX/ARA-C + Rituximab (R) (2nd part of R-hyper-CVAD) would be suitable under the current circumstance of CNS relapse of PMLBCL after frontline R-EPOCH (x6) and then R-ESHAP (x2) at relapse. You certainly need i.t. MTX=12mg (on day 2) and i.t. ARA-C=100mg (on day 8), as the disease will spread-if not already-into the leptomeninges. If response is good enough, you may also need to mobilize hematopoietic stem cells (CD34+) after R-HD-MTX/ARA-C if you have not done so after the 2nd R-ESHAP cycle, and therefore proceed to high-dose chemotherapy with BEAM + autologous stem cell transplantation (ASCT). Alternative high-dose chemotherapy regimens would be Busulfan/Melphalan (BuMel) or Thiotepa-Busulfan-Cyclophosphamide (TBC).
i.t. chemotherapy is required if disease has spread to the CNS and particularly in the leptomeninges, despite the fact that the patient will receive high-dose MTX & ARA-C, that are known to cross the BBB. I direct the attention of all participants in the current discussion to the original and follow-up publications of HD-MTX/ARA-C from M.D. Anderson investigators, where in the case of leptomeningeal involvement, i.t. MTX & ARA-C were administered until clearance of the CSF...!
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