Non-hodgkin's%20lymphoma Treatment

• CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone)
  • Recommended in the 1st-line treatment for PTCL and ATLL, and primary treatment of patients with cutaneous ALCL
  • In combination with Etoposide (CHOEP) is used in the 1st-line treatment of PTCL and ATLL
  • In combination with Obinutuzumab is recommended in the 1st- and 2nd-line treatment of FL
  • Part of the sequential chemoimmunotherapy of monomorphic and polymorphic PTLD if PET/CT scan is negative
• RCHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone)
  • Recommended in the 1st- and 2nd-line treatment of patients with FL, MZL, in the 1st-line treatment of primary mediastinal large B-cell lymphoma (PMBL) and DLBCL, and for concurrent chemoimmunotherapy of monomorphic and polymorphic PTLD
  • Recommended for aggressive induction therapy, alternating with RDHAP, for less aggressive induction, and in the 2nd-line and subsequent treatment of MCL
    • Dose-intensified CHOP (maxi-CHOP) alternating with Rituximab and high-dose Cytarabine (NORDIC regimen) is recommended for aggressive induction of MCL
  • Treatment option for HGBL
  • Combination with liposomal Doxorubicin (RCDOP) may be used as 1st-line treatment in DLBCL patients with poor LV function, frail or aged >80 years old with comorbidities
  • Used for patients with aggressive stage I/contiguous stage II (4-6 cycles), indolent noncontiguous stage II/III/IV, and aggressive noncontiguous stage II/III/IV NHL
  • Studies recommend a regimen of 3-6 cycles in patients with aggressive stage I and contiguous stage II NHL when given with IF-XRT
  • Studies have shown better treatment response (increased event-free survival and overall survival) to R-CHOP as compared to CHOP in advanced-stage DLBCL >60 years
• CVP (Cyclophosphamide, Vincristine and Prednisone/Prednisolone)
  • Recommended in the 1st-line treatment of MZL
  • Patients may be given Rituximab as maintenance therapy after treatment
  • In combination with Obinutuzumab is recommended in the 1st- and 2nd-line treatment of FL
  • Treatment option for frail patients with monomorphic (T-cell type) PTLD who are intolerant of anthracyclines
• R-CVP (Rituximab, Cyclophosphamide, Vincristine, and Prednisone)
  • Recommended for patients with indolent noncontiguous stage II/III/IV NHL, and in the 1st- and 2nd-line treatment of patients with FL and MZL
  • Treatment option for concurrent treatment of frail patients with monomorphic and polymorphic PTLD who are intolerant of anthracyclines
  • Addition of Gemcitabine (RGCVP) or Etoposide (RCEOP) to this combination may be used in patients as 1st-line treatment in DLBCL patients with poor LV function
    • RGCVP may also be used in patients >80 years old with comorbidities
    • RCEOP may be used as 2nd-line and subsequent therapy for patients with DLBCL and for concurrent treatment of frail patients with monomorphic and polymorphic PTLD who are intolerant of anthracyclines
• R-ACVBP (Rituximab, Cyclophosphamide, Doxorubicin, Vindesine, Bleomycin and Prednisone)
  • May be used for patients with aggressive stage I/contiguous stage II NHL
• EPOCH (Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin)
  • Recommended 1st-line therapy for ALCL, ATLL, hepatosplenic T-cell lymphoma and other peripheral T-cell lymphomas, 1st-line/additional treatment option for patients with HTCL, and primary treatment of patients with cutaneous ALCL
• EPOCH-R (Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin) + Rituximab (dose-adjusted)
  • Recommended in the following:
    • 1st-line treatment for patients with PMBL, DLBCL, PTCL, and Burkitt lymphoma
    • Induction therapy of patients with BL in combination with intrathecal Methotrexate
  • May also be used as 1st-line treatment in patients with DLBCL with poor LV function, for 2nd-line and subsequent treatment of DLBCL and for high-grade B-cell lymphomas (HGBL) with translocations of MYC and BCL2 and/or BCL6 or NOS
  • May be used as induction and 2^nd-line therapy for patients with BL
• SMILE (steroid [Dexamethasone], Methotrexate, Ifosfamide, Pegaspargase, Etoposide) (modified)
  • Recommended in the induction therapy of advanced stage EKNL
• For treatment regimens used in CLL/SSL, please see Chronic Lymphocytic Leukemia disease management chart for further information

• AspaMetDex (Pegaspargase, Methotrexate, Dexamethasone)
  • Induction therapy option of EKNL
• Bendamustine/Bortezomib, Rituximab
  • Treatment option for 2nd-line and subsequent treatment of MCL and MZL if no history of Bendamustine therapy
  • Bendamustine/Rituximab combination is a treatment option for aggressive and less aggressive induction of MCL
• CODOX-M (Cyclophosphamide, Doxorubicin, Vincristine, intrathecal Methotrexate and Cytarabine)
  • Followed by systemic Methotrexate and Rituximab, is recommended for induction therapy of patients <60 years old with low-risk BL
  • Followed by systemic Methotrexate alternating with Ifosfamide, Cytarabine, Etoposide and intrathecal Methotrexate (IVAC) + Rituximab, is recommended for induction therapy of patients <60 years with high-risk BL
  • Combination with Rituximab and Etoposide is recommended for induction therapy of patients with HGBL

• DHAX (Dexamethasone, Cytarabine, Oxaliplatin) ± Rituximab
  • Recommended in the 2nd-line and subsequent treatment of DLBCL and MCL, and 2nd-line therapy of patients with PTCL not otherwise specified, EATL, MEITL, AITL, ALCL and ATLL
  • 1st-line/additional treatment option for patients with HTCL
  • Also used for patients with relapsed/refractory ENKL

• ESHAP (Etoposide, Methylprednisolone, Cytarabine, Cisplatin) ± Rituximab
  • Recommended 2nd-line and subsequent treatment of patients with DLBCL, PTCL, not otherwise specified, EATL, MEITL, AITL, ALCL, ATLL and EKNL with Rituximab excluded

• FMC (Fludarabine, Mitoxantrone, Cyclophosphamide)
  • Indicated for T-PLL followed by Alemtuzumab

• GDP (Gemcitabine, Dexamethasone, Cisplatin/Carboplatin) ± Rituximab
  • Recommended 2nd-line and subsequent treatment for patients with DLBCL, PTCL, not otherwise specified, EATL, MEITL, AITL, ALCL, ATLL and EKNL with Rituximab excluded
  • Recommended in the induction therapy of EKNL in combination with Pegaspargase (DDGP) excluding Rituximab
  • May be used in the 2nd-line treatment of BL in combination with Rituximab

• Gemcitabine, Vinorelbine ± Rituximab
  • Treatment option in the 2nd-line and subsequent treatment of DLBCL

• GemOx (Gemcitabine, Oxaliplatin) ± Rituximab
  • Recommended 2nd-line and subsequent treatment for patients with MCL, DLBCL, PTCL not otherwise specified, EATL, MEITL, AITL, ALCL, ATLL and EKNL with Rituximab excluded
  • In combination with Pegaspargase with Rituximab excluded, is recommended in the induction therapy of EKNL

• GVD (Gemcitabine, Vinorelbine, liposomal Doxorubicin)
  • Recommended for 2nd-line and subsequent treatment of PTCL not otherwise specified, EATL, MEITL, AITL, ALCL, and ATLL
• HyperCVAD (hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone) + Rituximab
  • May be used as induction therapy for patients with MCL, <60-year-old patients with BL, and HGBL alternating with high-dose Methotrexate and Cytarabine + Rituximab
  • 1st-line alternative therapy for PTCL patients, for patients with ATLL and 1st-line/additional treatment option for patients with HTCL alternating with high-dose Methotrexate and Cytarabine

• Ibrutinib, Lenalidomide, Rituximab
  • Treatment option for refractory/relapsed MCL
• ICE (Ifosfamide, Carboplatin, Etoposide) ± Rituximab (RICE)
  • May be used in the 1st-line therapy of PMBL after RCHOP regimen, as 2nd-line and subsequent therapy for patients with DLBCL, as 2nd-line therapy for patients with BL in combination with Rituximab, and 2nd-line and subsequent therapy for PTCL not otherwise specified, EATL, MEITL, AITL, ALCL, ATLL and EKNL with Rituximab excluded (ICE)
  • Preferred 1st-line treatment option for patients with HTCL

• IVAC (Ifosfamide, Etoposide, Cytarabine)
  • 1st-line/additional treatment option for patients with HTCL
• IVE (Ifosfamide, Etoposide, Epirubicin)
  • 1st-line or additional therapy for patients with other PTCL histologies after CHOP alternating with intermediate-dose Methotrexate
• MINE (Mesna, Ifosfamide, Mitoxantrone, Etoposide) ± Rituximab
  • Recommended 2nd-line and subsequent treatment for patients with DLBCL

• Polatuzumab vedotin ± Bendamustine ± Rituximab
  • Recommended in the 2nd-line and subsequent treatment of patients with DLBCL with ≥2 previous treatments

• PEPC (Prednisone, Etoposide, Procarbazine, Cyclophosphamide) ± Rituximab
  • May be used as 2nd-line therapy in patients with MCL and as 1st-line, 2nd-line and subsequent therapy in patients with DLBCL and those with poor LV function
  • May also be used for frail patients intolerant of anthracycline with monomorphic and polymorphic PTLD

• RBAC (Rituximab, Bendamustine, Cytarabine)
  • Treatment option for less aggressive induction of MCL or as 2nd-line and subsequent therapy of MCL if not previously given

• RDHAP (Rituximab, Dexamethasone, Cytarabine) + platinum (Carboplatin, Cisplatin or Oxaliplatin)
  • Recommended for aggressive induction therapy of patients with MCL, alternating with RCHOP, as 2nd-line and subsequent therapy for patients with DLBCL, and 2nd-line and subsequent therapy for PTCL not otherwise specified, EATL, MEITL, AITL, ALCL, ATLL and ENKL with Rituximab excluded (DHAP)
  • 1st-line/additional treatment option for patients with HTCL

• R-FCM (Rituximab, Fludarabine, Cyclophosphamide and Mitoxantrone)
  • Recommended for patients with indolent noncontiguous stage II/III/IV NHL
  • Combination without Rituximab may be used as 1st-line therapy for symptomatic T-PLL

• RIVAC (Rituximab, Ifosfamide, Cytarabine, Etoposide)
  • May be used in the 2nd-line treatment of BL
• VR-CAP (Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone)
  • Treatment option for less aggressive induction and in the 2nd-line treatment of MCL

• Eg Bendamustine, Chlorambucil, Cyclophosphamide, Ifosfamide, Temozolomide
• May be used in combination with Vincristine, Prednisone, Dexamethasone, Rituximab, Procarbazine, Doxorubicin, or Fludarabine for patients with indolent noncontiguous stage II/III/IV NHL
• Recommended as 1st line treatment for elderly patients with FL with or without Rituximab
• Temozolomide is recommended for refractory/relapsed MF/SS with CNS involvement
• May be given with or without corticosteroids

• May be used alone or in combination with Rituximab in the 2nd-line treatment of MCL
  • Bendamustine/Rituximab combination may be used as 1st-line therapy in patients with MZL and 2nd-line and subsequent therapy in patients with DLBCL and MZL
• Alternative treatment option for 2nd-line and subsequent therapy of PTCL not otherwise specified, EATL, MEITL, AITL, ALCL and ATLL

• Combination with Rituximab is used in the 1st- and 2nd-line therapy for elderly or infirm patients who cannot tolerate any treatment regimens for FL and MZL
• Recommended for relapsed/refractory MF/SS

• Treatment option in the 1st- and 2nd-line therapy of elderly or infirm patients who cannot tolerate other treatment regimens for FL and MZL when given in combination with Rituximab 
• Recommended for relapsed/refractory MF/SS 
• Alternative 2nd-line and subsequent therapy for patients with or initial palliative intent treatment for PTCL not otherwise specified, EATL, MEITL, AITL, ALCL who are against organ transplant

• Recommended as 3rd-line and subsequent therapy after ≥2 lines of systemic therapy in patients with relapsed or refractory large B-cell lymphoma, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from FL
• Used in the treatment of DLBCL and nodal MZL, after ≥2 previous chemoimmunotherapy regimens

• Recommended for adult patients with relapsed or refractory MCL only after chemoimmunotherapy and BTK inhibitor

• Indicated for adult patients with relapsed or refractory large B-cell lymphoma after ≥2 lines of systemic therapy, including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and FL grade 3B
• Used in the treatment of DLBCL arising from nodal MZL, after ≥2 previous chemoimmunotherapy regimens

• Recommended in the 2nd-line and subsequent treatment of adult patients with relapsed or refractory large B-cell lymphoma after ≥2 lines of systemic therapy including DLBCL, NOS and high-grade B-cell lymphoma and DLBCL arising from FL, as 3rd-line and subsequent treatment of patients with FL, and for patients with relapsed or refractory FL after ≥2 lines of systemic therapy
• Used in the treatment of DLBCL arising from FL and nodal MZL, after ≥2 previous chemoimmunotherapy regimens

• Eg 2-Chlorodeoxyadenosine, Cladribine, Cytarabine, Fludarabine, Gemcitabine, Methotrexate, Pentostatin, Pralatrexate, Tazemetostat
• Recommended for patients with indolent noncontiguous stage II/III/IV NHL
• Cladribine is a purine analog recommended for initial therapy of HCL and for relapsed/refractory disease with or without Rituximab 
• Cytarabine when combined with Rituximab may be used as 2nd-line therapy for patients with relapsed BL 
• Fludarabine may also be combined with Chlorambucil
• Gemcitabine is recommended in the systemic 1st-line therapy of MF/SS and as 2nd-line and subsequent therapy for patients with PTCL not otherwise specified, EATL, MEITL, AITL, ALCL and ATLL
• Methotrexate may be used as primary treatment of patients with MF/SS, primary treatment of patients with cutaneous ALCL, and 2nd-line systemic therapy for DLBCL with CNS disease
• Pentostatin is a purine analog recommended for initial therapy and relapsed/refractory HCL disease with or without Rituximab and may be used as a treatment option for patients with relapsed/refractory MF/SS
• Pralatrexate (preferred) and Gemcitabine are 2nd-line and subsequent therapies for patients with PTCL not otherwise specified, EATL, MEITL, AITL, ALCL, ATLL, systemic 1st-line therapy for patients with MF/SS, and primary treatment of patients with cutaneous ALCL
  • Pralatrexate is also recommended for relapsed/refractory EKNL
• Tazemetostat is a 2nd-line therapy option for elderly or infirm FL patients with EZH2 wild-type or unknown relapsed/refractory disease who have no satisfactory alternative treatment options) and 3rd-line and subsequent therapy option for patients with EZH2 mutation-positive and those with EZH2 wild-type or unknown relapsed/refractory FL who have no satisfactory alternative treatment options

• Treatment option for relapsed/refractory MF/SS

• Used in the 2nd-line and subsequent treatment of MCL as monotherapy or in combination with Rituximab
• Recommended in the 2nd-line and subsequent therapy of patients with ATLL and as an alternative 2nd-line and subsequent therapy for patients with PTCL not otherwise specified, EATL, MEITL and AITL
• Treatment option for the following:
  • 2nd-line treatment of patients with FL where anti-CD20 monoclonal antibody treatment is not appropriate
  • 1st-line consolidation therapy in patients aged 60-80 years with DLBCL
  • 1st- and 2nd-line treatment of FL and MZL given in combination with Rituximab; combination with Obinutuzumab may also be used; combination with Tafasitamab may be considered in patients with histologic transformation to DLBCL
  • Treatment option in the 1st-line therapy of MZL and in the 2nd-line and subsequent treatment of patients with non-GCB DLBCL given in combination with Rituximab
    • 2nd-line and subsequent treatment of MZL particularly in elderly and infirm patients who are intolerant of other treatment regimens given in combination with Rituximab

• Systemic therapy option for stage IB-IV MF, and stage IVA1-IVA2 SS

• Systemic therapy option for stage IB-IIA, III MF, stage IVA1-IVA2 SS and relapsed/refractory MF/SS
• Second-line and subsequent treatment option for PTCL not otherwise specified, EATL, MEITL and AITL patients who are against organ transplant, ATLL, for symptomatic management of T-PLL patients (IV route with or without Pentostatin), 1st-line/additional treatment option for patients with HTCL (with or without Pentostatin), and as additional therapy in patients with T-LGLL unresponsive to 1st-line therapy 

• Second-line and subsequent treatment option for PTCL, CD30-positive ATLL, ENKL, AITL and DLBCL patients, and systemic 1st-line therapy for patients with MF/SS and primary treatment of patients with cutaneous ALCL
• In combination with CHP (Cyclophosphamide, Doxorubicin, Prednisone) is recommended for monomorphic (T-cell type) PTLD, 1st-line therapy of PTCL, initial therapy of ATLL, primary treatment of patients with cutaneous ALCL, and 1st-line/additional treatment option for patients with HTCL

• May be an option in the 1st-line consolidation/extended dosing and 2nd-line treatment of FL and 1st- and 2nd line and subsequent treatment of MZL
• May be used as 2nd-line therapy of PCBCL, leg type

• Alternative 3rd-line and subsequent therapy option for patients with relapsed/refractory DLBCL previously given ≥2 lines of systemic therapy
• Used in the treatment of DLBCL arising from FL and nodal MZL, after ≥2 previous chemoimmunotherapy regimens

• Recommended in the 2nd-line and subsequent therapy of patients with ATLL and systemic 1st-line therapy of MF/SS

• Recommended for progressive HCL after relapsed/refractory treatment

• Monotherapy or in combination with Brentuximab vedotin is a treatment option for relapsed/refractory PMBL and EKNL

• Recommended for FL patients in the 1st- and 2nd-line consolidation or extended dosing therapy and in the 2nd-line and subsequent treatment in combination with Bendamustine, CHOP or CVP, of patients with Rituximab-refractory disease

• Recommended in the following:
  • 2nd-line consolidation or extended dosing treatment for Rituximab-refractory disease of patients with B-cell lymphomas
• Needs further studies to be proven effective for patients with indolent noncontiguous stage II/III/IV NHL

• Indicated for patients with relapsed/refractory PMBL, EKNL and stage IB, III, IV MF/stage IVA1-IVA2 SS and refractory/relapsed MF/SS requiring systemic therapy

• First-line therapy for patients with indolent noncontiguous stage II/III/IV CD20-positive NHL
  • May be combined with other chemotherapeutic drugs (Bendamustine, Cladribine, Fludarabine, Cyclophosphamide, Vincristine, Prednisone, Doxorubicin, Mitoxantrone)

• Recommended in the following:
  • For patients with indolent stage I and contiguous stage II NHL
    • Considered in patients with contraindications for radiotherapy, and for those unresponsive to other chemotherapeutic agents and interventions
  • 1st- and 2nd-line treatment of patients with FL and for elderly or infirm patients who cannot tolerate other treatment regimens for FL and MZL
  • 1st- and 2nd-line consolidation or extended dosing therapy of patients with FL and as 1st-line extended therapy for MZL
  • 1st-line therapy of patients with splenic, extranodal (MALT) and nodal MZL and for the sequential chemoimmunotherapy of monomorphic (B-cell type) and polymorphic PTLD
  • Initial therapy option for patients with PCBCL with generalized disease 
  • Maintenance therapy of MCL patients after high-dose autologous stem cell rescue or less aggressive therapy
  • In combination with high-dose Methotrexate for primary CNS PTLD (B-cell type)
• Treatment option in the following:
  • 1st-line therapy of patients with extranodal MALT and nodal MZL
  • 2nd-line/subsequent therapy of patients with MZL with longer duration of remission and for DLBCL
  • Refractory/relapsed HCL

• Also recommended for patients with indolent NHL in relapse
  • Studies show a response rate of 40-50% in patients with indolent NHL
  • May also be combined with other chemotherapeutic drugs

• Several studies have shown that maintenance therapy with Rituximab improves overall survival in FL patients

• Used as 2nd-line and subsequent therapy for patients with relapsed/refractory DLBCL with contraindication to transplant, in combination with Lenalidomide
• Also used in the treatment of DLBCL arising from FL and nodal MZL when transplant is contraindicated and no response to treatment or with disease progression after chemoimmunotherapy

• Eg Acalabrutinib, Alectinib, Belinostat, Bortezomib, Copanlisib, Crizotinib, Duvelisib, Ibrutinib, Idelalisib, Romidepsin, Selinexor, Umbralisib, Vemurafenib, Venetoclax, Vorinostat, Zanubrutinib
• There are ongoing studies investigating the use of these drugs for other types of cancer

• Recommended in the 2nd-line and subsequent treatment of patients with MCL

• Treatment option in the 2nd-line and subsequent treatment of patients with ALK-positive ALCL

Belinostat

• Has been approved for the treatment of relapsed/refractory PTCL and as an alternative 2nd-line and subsequent therapy for ATLL, PTCL not otherwise specified, EATL, MEITL, AITL, ALCL and relapsed/refractory EKNL

Bortezomib

• May be used alone or in combination with Rituximab as 2nd-line therapy of patients with MCL, treatment option for relapsed/refractory MF/SS, as 2nd-line and subsequent therapy for PTCL patients who are against organ transplant, and for ATLL

• Treatment option in the 2nd-line and subsequent therapy of patients with refractory/relapsed MZL, after 2 previous treatments and 3rd-line and subsequent therapy for patients with FL

• Treatment option in the 2nd-line and subsequent treatment of patients with ALK-positive ALCL

• Treatment option in the 2nd-line and subsequent therapy of patients with relapsed/refractory MZL, after 2 previous treatments
• An alternative 2nd-line and subsequent therapy for PTCL not otherwise specified, EATL, MEITL, AITL, ALCL

• Recommended in the following:
  • 2nd-line and subsequent treatment of patients with MCL with short response duration to previous chemoimmunotherapy; may be combined with Rituximab or Venetoclax
  • 2nd-line and subsequent treatment of MZL
    • One of the preferred regimens for elderly or infirm patients who cannot tolerate other treatment regimens
• Treatment option in the 2nd-line and subsequent treatment of non-germinal center B-cell (GCB) DLBCL and in the treatment of progressive HCL after relapsed/refractory therapy
• Associated with transient increase in lymphocyte count, grade 2 bleeding and hypertension

• Treatment option in the 2nd-line and subsequent therapy of patients with relapsed/refractory MZL, after 2 previous treatments

Romidepsin

• Indicated for patients with cutaneous T-cell lymphoma, 2nd-line and subsequent therapy of PTCL not otherwise specified, EATL, MEITL, and  AITL, and 1st-line systemic therapy for patients with MF/SS or in relapsed/refractory EKNL

Selinexor

• A 3rd-line and subsequent therapy option for patients with DLBCL after ≥2 previous systemic treatments

Vemurafenib

• Recommended in relapsed/refractory HCL and progressive disease after treatment of relapsed/refractory HCL

• Treatment option in the 2nd-line treatment of MCL with or without Rituximab or Ibrutinub

Vorinostat

• Recommended in the systemic 1st-line therapy of MF/SS

Zanubrutinib

• Recommended in the 2nd-line and subsequent treatment of patients with MCL and relapsed/refractory MZL after at least 1 prior anti-CD20-mAB-based regimen

Skin-directed Therapeutic Agents

• Used for primary cutaneous B-cell and T-cell lymphomas
• Recommended topical agents include Carmustine, corticosteroids, Imiquimod, Mechlorethamine, and retinoids (eg Acitretin, Bexarotene, Isotretinoin, Tazarotene)
  • For generalized skin involvement: Corticosteroids, Mechlorethamine

Other Therapeutic Agents

• Zidovudine may be used as 1st-line therapy for acute or chronic/smoldering ATLL, as additional therapy for acute ATLL if no response after initial treatments
• Arsenic trioxide may be used as 2nd-line and subsequent therapy for ATLL
• Interferon alfa/gamma-1b is a systemic therapy option of patients with MF/SS and primary treatment of patients with cutaneous ALCL and 1st-line therapy for acute or chronic/smoldering ATLL, as additional therapy for acute ATLL if no response after initial treatments
• Peginterferon-alfa 2a may be used in relapsed/refractory HCL

• Most common forms in NHL patients include autoimmune hemolytic anemia, immune thrombocytopenic purpura and pure red blood cell aplasia
• Treatment includes administration of corticosteroids; Rituximab, intravenous immunoglobulin (IVIg), or Cyclosporin may be given for patients unresponsive to corticosteroid therapy and Eltrombopag or Romiplostim may be used for the treatment of thrombocytopenia in patients with ITP refractory to steroids, IVIg or splenectomy
  • Splenectomy may also be considered for steroid-refractory patients

• Occurs in 25% of patients undergoing treatment with Alemtuzumab
• Increased risk of reactivation in patients receiving Fludarabine-based chemotherapy or Idelalisib
• Prophylaxis with Ganciclovir may be considered in patients with increasing viral load during treatment

Hepatitis B Virus

• Increased risk for HBV reactivation in patients undergoing treatment with anti-CD20 monoclonal antibody
• Prophylaxis with Entecavir is recommended for patients on immunosuppressive cytotoxic therapy with positive Hepatitis B surface antigen (HBsAg), HBsAg negative but Hepatitis B core antibody (HBcAb) positive, or elevated HBsAb levels with increasing HBV DNA load
  • Lamivudine is not recommended as alternative due to increased risk of developing resistance
  • Adefovir, Telbivudine and Tenofovir may be used as alternatives to Entecavir

• Viral load should be monitored using PCR monthly during and every 3 months after treatment
• Prophylactic regimen should be continued until 12 months after NHL treatment

• Most frequently occurs in NHL patients with B-cell lymphomas (eg DLBCL, MZL)
• Patients may be initially treated with antivirals (eg Pegylated interferon, Ribavirin, Telaprevir, Boceprevir)
  • Direct acting antivirals may be combined with triple antiviral therapy in asymptomatic patients with low-grade B-cell NHL and hepatitis C infection

• Patients with NHL are at increased risk for skin dissemination of localized viral infections such as HSV and VZV
• For patients with frequent recurrence of HSV infection, prophylaxis with Acyclovir or equivalent should be considered

• A demyelinating disease caused by the latent John Cunningham (JC) polyoma virus which infects the CNS in immunocompromised patients
• Administration of Brentuximab vedotin and Rituximab is associated with increased risk of developing PML
• There is currently no effective treatment for PML, thus prevention is highly advised
  • Monitoring of signs and symptoms and CSF analysis using PCR is recommended

• Referral to a dermatologist is recommended
• Use of mild/unscented soap, moisturizers and emollients may help with skin dryness
• Treatment options include:
  • 1st line: Antihistamines, Gabapentin, Pregabalin
  • 2nd line: Aprepitant, Mirtazapine, selective serotonin reuptake inhibitors (SSRIs)
  • 3rd line: Naltrexone, systemic corticosteroids

• An immune response composed of splenomegaly, fever, rashes, painful lymphadenopathy and bone pain
• Commonly occurs in CLL patients undergoing Lenalidomide treatment
• Corticosteroid administration is recommended for management of inflammation and lymphadenopathy
• Antihistamines may be used to manage pruritus with rashes
• Prophylaxis may be considered for patients on Lenalidomide treatment who may be predisposed to tumor flare reactions

• Cellular destruction secondary to chemotherapy causing hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, which may lead to acute renal failure
  • Appears 12-72 hours after initiation of chemotherapy

• Prophylaxis prior to chemotherapy is recommended especially for patients treated with Venetoclax, Lenalidomide or Obinutuzumab and for patients with histologies of BL and LL
  • May give Allopurinol or Febuxostat prior to initiation of chemotherapy to control uric acid levels
  • Rasburicase is recommended for patients with hyperuricemia unresponsive to Allopurinol, acute renal failure, patients with high bulk disease in urgent need of treatment, or if proper hydration is difficult

• Monitor serum electrolytes, renal function and cardiac function should be monitored regularly; proper hydration is advised

Venous Thromboembolism

• May be prevented by administration of low-dose Aspirin in patients with severely increased platelet or patients receiving Lenalidomide

Phototherapy

• Eg ultraviolet B (UVB), narrowband UVB (NB-UVB), Psoralen plus ultraviolet A (PUVA), ultraviolet A1 (UVA1)
• Skin-directed treatment option for patients with MF/SS
• UVB is NB-UVB is recommended for limited/localized skin involvement
• UVB, NB-UVB, PUVA, or UVA1 may be used for generalized skin involvement

Extracorporeal Photopheresis (ECP)

• Primarily reserved for patients with uncommon MF/SS with low level blood involvement