Introduction

• It is a general term used to denote monoclonal proliferation of lymphoid cells, excluding Hodgkin Lymphoma.

Epidemiology

• Incidence – 30 /1 lac population
• Usually seen after age of 60 years.
• Death rate- 7/1lac/year
• 7th leading site of new cancer cases, accounting for 4% of all cases
• Increased incidence is seen in recent years. It has paralleled a major decrease in mortality from other causes.

Etiopathogenesis

• Infectious agents
  • Epstein Barr virus
    • In latent phase of infection (when virus enters the cell and remains in DNA) transformation of reacting B-cells into proliferating blasts occurs.
    • Lymphoid tumors associated with infection with EBV
      • Burkitt Lymphoma
      • Post organ transplant lymphoma
      • Primary CNS diffuse large B cell lymphoma
      • Hodgkin disease
      • Extranodal NK/T cell lymphoma, nasal type.
      • Primary effusion lymphoma
      • Oral cavity plasmablastic lymphoma
  • HTLV I
    • 3-5% infected people develop T cell malignancy (Adult T cell leukemia lymphoma) after 40-60 years of latency
    • Tax protein, encoded & expressed by activated form of HTLV-1, rescues Virus expressing T cells from apoptotic death
  • KSHV (HHV-8)
    • Causes primary effusion lymphoma and multicentricCastleman disease.
    • It encodes putative oncogenes and genes that stimulate angiogenesis and cell proliferation
      • G protein coupled receptor – promoting cell transformation & angiogenesis.
      • IL6 homologous cytokine-prevents cell apoptosis in IL6 dependent cell lines.
    • It also encodes a Cyclin D homologue – K Cyclin, which promotes viral oncogenesis.
  • HIV
    • HIV associated lymphomas include
      • Diffuse large B cell lymphoma
      • Burkitt lymphoma
  • Hepatitis C Virus- It causes 
    • Lymphoplasmacytic lymphoma
    • Splenic marginal zone lymphoma
    • DLBCL
    • Nodal marginal zone lymphoma
  • H. Pylori- It causes gastric MALT lymphoma
  • B. burgdorferi- Causes cutaneous MALT lymphoma
  • Chlamydia psittaci- Causes ocular adnexalMALToma
  • Campylobacterjejuni- Intestinal MALToma with alpha heavy chain disease
•  Inherited immunodeficiency disease
  • Klinefelter’s syndrome
  • Chediak – Higashi syndrome
  • Ataxia telangiectasia syndrome
  • Wiscott-Aldrich syndrome
  • Common variable immunodeficiency disease
  • Severe combined immunodeficiency
• Acquired immunodeficiency diseases
  • Iatrogenic immunosuppression
  • HIV -1 infection
  • Acquired hypogammaglobulinemia
• Autoimmune disease
  • Sjogren syndrome
  • Celiac sprue
  • Rheumatoid arthritis and systemic lupus erythematosus
  • Hashimoto’s thyroiditis
• Chemical or Drug exposures
  • Phenytoin
  • Dioxin, phenoxy herbicides
  • Radiation
  • Prior chemotherapy and radiation  therapy
  • Benzidine
  • Minerals
  • Lubricating oils
  • Pesticides and herbicides
  • Wood dust

Classifications of NHL (These are old classifications which are no more used. Presently WHO classification is used which is based on immunophenotyping and genetic abnormalities. There is no entity called Non-Hodgkin’s Lymphoma in present WHO classification.)

• Rappaport classification
• Lukes Collins Classificaion 
• Kiel Classification
• Working Formulations for Clinical Usage
• Real Classification 

Clinical Features

• Generalized lymphadenopathy
  • Discrete, painless, and firm
  • Nodes along the central axis are more commonly involved
  • Epitrochlear node involvement is seen especially in NHL
• Extranodal involvement is commonly seen in NHL compared to HL
  • Symptoms and signs depend on organ involved
  • Commonly affected organs are bone marrow, nasopharynx, tonsils, gut, thyroid, lung, skin, testis and brain
• Hepato-splenomegaly
• B symptoms
  • Fever with drenching sweating
  • Pruritus
  • Weight loss

Investigations

• Lymph node biopsy and immunohistochemistry
• Hemogram
  • Normocytic normochromic anemia
  • Late cases (Due to marrow involvement)- thrombocytopenia andneutropenia
  • Sometimes tumor cells may be seen in the peripheral blood
• Serum LDH level – elevated
• Serum uric acid level – elevated
• Chest X-ray, CT, MRI –for staging
• Bone marrow aspiration / trephine biopsy- Paratrabecular lymphoid aggregates if involved
• HIV testing

Staging (Ann Arbor with Luganomodification- Simplified)- For primary nodal lymphomas

• Tonsils, Waldeyer's ring and spleen are considered nodal tissue
• For PET avid histological subtypes, whole body PET CT is preferred modality of imaging. For non-avid histological subtypes also PET is preferred as it can pick up sites with histological transformation.
• Stage- I- Single lymph node region or a group of adjacent nodes / single extra lymphatic site without nodal involvement
• Stage II- 2 or more lymph node regions on same side of diaphragmOrSingle  extra lymphatic site with limited contiguous lymph node site
• Stage III- 2 or more lymph node regions on both sides of diaphragm or Nodes above the diaphragm with spleen involvement
• Stage IV- Nodes on both sides of diaphragm with additional non-contiguous extra-lymphatic involvement

• Suffix
  • A- No systemic symptoms
  • B- Associated with weight loss, Drenching sweats & fever
  • E-for extra nodal involvement
  • S- for splenic involvement

Assessment of response with PET CT scan: Lugano Response criteria (Simplified): 

• PET 5 point scale

 1- No uptake above background

2- Uptake ≤ mediastinum

3- Uptake >mediastinum but ≤ liver

4. Uptake moderately >liver

5. Uptake markedly higher than liver and/or new lesions

X- New areas of uptake unlikely to be related to lymphoma

• Complete response:
  • Score of 1, 2 or 3 with or without residual mass
  • Target nodes or nodal masses must regress to ≤ 2.5cm in the longest diameter of the lesion.
  • If organ is involved- 50% reduction in size of organ
  • No extralymphatic site of disease
• Partial response: (At the interim, it indicates responding disease and at the end of therapy, it indicates residual disease)
  • Score of 4 or 5, with reduced uptake compared with baseline
  • Sum of product of the perpendicular diameters of multiple lesions (SPD)- >50% reduction
  • No new progressive lesions
• No response: PET same as done at diagnosis
• Progressive disease: Increased intensity/ new lesions

Prognosis

• International Prognostic Index for Non-Hodgkin’s Lymphoma: Five clinical risk factors
  • Age- > 60 years
  • Serum lactate dehydrogenase levels elevated
  • Poor performance status 
  • Ann Arbor stage III or IV
  • Extranodal involvement
• Prognosis in general
  • Indolent malignancies are not curable
  • Aggressive malignancies have long disease free survival after initial therapy and are potentially curable

Treatment: Depends on type of malignancy

Commonly used chemotherapy protocols:

• Rituximab
  • Inj. Rituximab- 375mg/m2- in 500ml NS over 4 hrs.
  • Premedicate with Avil and Hydrocortisone
  • 100mg in 100ml is administered as test dose prior to actual dose.
  • Usually given prior to actual chemotherapy.
• CHOP
  • Frequency: 21 days
  • Inj. Cyclophosphamide- 750mg/m2 in 500ml D5% over 2 hrs- On Day 1
  • Inj. Doxorubicin- 50mg/m2 in 100ml NS over 30min- On Day 1
  • Inj. Vincristine- 1.4mg/m2 (Max- 2mg) in 100ml NS over 10min- On Day 1
  • Tab. Prednisolone- 40mg/m2- From Day 1 to Day 5 (5 days)
  • Dose adjustments:

• CVP
  • Frequency: 21 days
  • Inj. Cyclophosphamide- 750mg/m2 in 500ml D5% over 2 hrs- On Day 1
  • Inj. Vincristine- 1.4mg/m2 (Max- 2mg) in 100ml NS over 10min- On Day 1
  • Tab. Prednisolone- 40mg/m2- From Day 1 to Day 5 (5 days)
  • Dose adjustments:

• CHOEP
  • Frequency: 21 days
  • Inj. Cyclophosphamide- 750mg/m2 in 500ml D5% over 2 hrs- On Day 1
  • Inj. Doxorubicin- 50mg/m2 in 100ml NS over 30min- On Day 1
  • Inj. Vincristine- 1.4mg/m2 (Max- 2mg) in 100ml NS over 10min- On Day 1
  • Inj. Etoposide- 100mg/m2 in 500ml NS over 1hr- From Day 1 to Day 3 (3 days)
  • Tab. Prednisolone- 40mg/m2- From Day 1 to Day 5 (5 days)
  • Inj. G-CSF- 300mcg- SC- OD- From day 6
  • Dose adjustments:

• Bendamustine:
  • Frequency: 28 days
  • Inj. Bendamustine- 90mg/m2 in 500ml NS over 1 hr- On day 1 and Day 2 (2 days)
  • Dose adjustments: 
    • ANC <1000/cmm or Platelet count <75,000/cmm- Delay until ANC >1000/cmm or Platelet count >75,000/cmm and give at 50mg/m2 for all subsequent cycles
    • If recurrence of cytopenia despite of decreased dose- Delay until ANC >1000/cmm or Platelet count >75,000/cmm and give at 25mg/m2 for all subsequent cycles
    • Bilirubin (mg/dL)
    • 1.5-3- Give 30% of dose
    • >3- Omit
• FC
  • Frequency: 28 days
  • Inj. Fludarabine- 25mg/m2- in 100ml NS over 30min- From Day 1 to Day 3 (3 days)
  • Inj. Cyclophosphamide- 250mg/m2- in 250ml D5% over 1hr- - From Day 1 to Day 3 (3 days)
  • Dose adjustments:

• Cladribine
  • Frequency: Only once
  • Inj. Cladribine- 3.6mg/m2 in 500ml NS over 24 hrs- From Day 1 to Day 7 (Continuous infusion for 7 days)
  • Dose adjustments:
    • Creatinine clearance (ml/min)
      • 30-70- Give 60% of dose
      • <30- Do not give
• CODOX-M- IVAC
  • For High risk patients (any 2 of following- Raised LDH, WHO performance score 2-4, Stage- III/IV, More than 1 extranodal site)- Give alternate CODOX-M and IVAC for 4 cycles (i.e- CODOX-M- IVAC- CODOX-M- IVAC)
  • For low risk patients- Give 3 courses of CODOX-M
  • Frequency: Give next cycle after marrow recovery
  • CODOX-M
    • Inj. Doxorubicin- 40mg/m2- in 100ml NS over 30min- on Day 1
    • Inj. Vincristine- 1.5mg/m2 (Max-2mg)- in 100ml NS- over 10 min- on Day 1 and Day 8
    • Inj. Cyclophosphamide- 800mg/m2 in 250ml NS over 1hr- On day 1
    • Inj. Cyclophosphamide- 200mg/m2 in 250ml NS over 1hr- from Day 2 to Day 5 (4 days)
    • Inj. Cytarabine- 70mg- Intrathecal- On day 1 and Day 3 (2 doses)
    • On Day 9 start Hydration
    • Hydration- ½ NS/ NS with 6 amp NaHCO3- 125ml/m2/hr till end of last Folinic acid (Start chemo after at least 12hrs of hydration)
    • Measure urine pH after 6 hrs of hydration. Start chemo once urine pH is >7.
    • Inj. Methotrexate- 300mg/m2 in 100ml NS over 1hr
    • Inj. Methotrexate- 2700mg/m2- in 500ml NS over next 23 hrs
    • Inj. Folinic acid- 30mg- IV- Bolus- 6 hrly for 6 doses- Start at 36hrs of starting methotrexate infusion.
    • Inj. Methotrexate- 12.5mg- Intrathecal stat- Tab. Folinic acid 15mg—24hrs after IT-MTX
    • G-CSF- 300mcg- SC- OD- from Day 13 till ANC >1500/cmm
    • Dose modifications:
      • No dose modifications for haematological toxicity

• IVAC
  • Inj. Etoposide- 60mg/m2- in 500ml NS over 1hr from Day 1 to Day 5.
  • Inj. Ifosfamide 1.5gm/m2 min 500ml NS over 15min from Day 1 to Day 5
  • Inj. Mesna 300mg/m2- IV Bolus at 0, 4 and 8Hrs from Day 1 to Day 5
  • Inj. Cytarabine- 2gm/m2 in 500ml NS over 3 hrs- BD- On Day 1 and Day 2. (4 doses)
  • Inj. Methotrexate- 12.5mg- Intrathecal stat- Tab. Folinic acid 15mg—24hrs after IT-MTX
  • G-CSF- 300mcg- SC- OD- from Day 7 till ANC >1500/cmm
  • Prednisolone eye drops- QID
  • Dose modifications
    • No dose modifications for haematological toxicity
    • If patient develops neurotoxicity- Stop ifosfamide and give methylene blue.

Salvage protocols

• GCD
  • Frequency: 21 days
  • Inj. Gemcitabine- 1000mg/m2- in 250ml NS over 30 min- on Day 1 and Day 8
  • Inj. Carboplatin- 5X(25+Creatinine clearance)- Maximum- 800mg- in 500ml D5% over 1hr- On day 1
  • Inj. Dexamethasone- 40mg in 100ml NS over 1 hr- From Day 1 to Day 4
  • Dose adjustments:
    • Drug induced pneumonitis- Discontinue treatment

• ICE
  • Frequency: 21 days
  • Inj. Etoposide- 100mg/m2- in 500ml NS over 2 hrs- From Day 1 to Day 3 (3 days)
  • Inj. Carboplatin- 5X(25+Creatinine clearance)- Maximum- 800mg- in 500ml D5% over 1hr- On Day 2
  • Inj. Ifosfamide- 5000mg/m2 + Mesna- 5000mg/m2 in 1 lit D5% over 24hrs- On Day 2
  • Tab. Phenytoin- 300mg- PO- OD from Day 1
  • Inj. G-CSF- 300mcg- SC-OD from Day 5
  • Dose adjustments:

• DA-EPOCH
  • Frequency: 21 days
  • Inj. Etoposide- 50mg/m2- in 500ml NS over 24 hours- From Day 1 to Day 4 (4 days)
  • Inj. Doxorubicin 10mg/m2 + Vincristine- 0.4mg/m2 in 500ml NS over 24 hours - From Day 1 to Day 4 (4 days)
  • Inj. Cyclophosphamide- 750mg/m2 in 500ml D5% over 3 hours- on Day 5
  • Tab. Prednisolone- 60mg/m2-OD- From Day 1 to Day 5.
  • Inj. G-CSF- 300mcg- SC- OD- From day 6 until ANC >5000/cmm
  • Intrathecalmethotrexate- 12 mg- on days 1 and 5 of cycles 3-6.
  • Following chemotherapy, measure CBC twice a week. Adjust the dose as below
    • ANC nadir - >500/cmm- Increase doses of etoposide, doxorubicin and cyclophosphamide by 20% of those on the previous cycle
    • ANC nadir - <500- Do not change the dose
    • Platelet count nadir- <25,000- Decrease doses of cyclophosphamide by 20%of those on the previous cycle 
  • Dose adjustments:

• DHAP
  • Frequency: 28 days
  • Tab. Dexamethasone- 40mg- OD- From Day 1 to Day 4
  • Pre-hydration- 1000ml NS with 20 mEqKCl- Infuse over 3 hrs + Tab. Frusemide- 40mg - Stat
  • Inj. Cisplatin- 100mg/m2- in 1000ml NS over 24 hrs on Day 1
  • Post-hydration
    • 1000ml NS with 20mEq KCl- over 3hrs
    • 1000ml NS with 1gm MgSO4- over 6hrs
    • 1000ml NS  over 6hrs
    • 1000ml NS with 20mEq KCl- over 6hrs
    • 1000ml NS  over 6hrs
    • 1000ml NS with 20mEq KCl- over 6hrs
  • Inj. Cytarabine- 2000mg/m2 in 500ml NS over 3 hrs- BD- On day 2 (2 doses)
  • Prednisolone eye drops- 4 times a day
  • Inj. G-CSF- 300mcg- SC-OD from day 5
  • Dose adjustments:
    • ANC- <1000/cmm or Platelet count- <1,00,000/cmm- Delay until ANC- >1000/cmm and Platelet count- >1,00,000/cmm
    • Creatinine clearance- <50ml/min- No DHAP to be given
    • Bilirubin- >2 gm/dL- Give 50% dose of Cytarabine.

Radiotherapy:

• Definitive treatment: (1.5-2 Gy daily fractions)
  • Follicular lymphoma, Marginal zone lymphoma, Gastric lymphoma - 24-30 Gy
  • Mantle cell lymphoma- 24-36 Gy
  • DLBCL, High grade B cell lymphomas- 36- 50 Gy
• Palliative RT
  • 2 Gy X 2 fractions. May be repeated if required. Maximum dose up to 30 Gy.

R-LMB Intergroup B NHL 2010 trial protocol (For children and adolescents)- Though designed for Burkiit’s lymphoma, this protocol is used for all high grade NHL such as DLBCL. For primary mediastinal lymphoma give R-DA-EPOCH.

Protocol is given as follows

• Prephase - 1 cycle of COP
• Induction-
  • If CNS negative- 2 Cycles of R-COPADM (MTX- 3gm/m2)
  • If CNS positive/ Burkitt lymphoma- 2 cycles of R-COPADM2 (MTX- 8gm/m2)
• Consolidation-
  • If CNS negative- 2 cycles of R-CYM (After 1^st cycle, do PET CT- If positive- Treat as per CNS positive case/ Burkitt lymphoma)
  • If CNS positive/ Burkitt lymphoma- 2 cycles of R-CYVEwith HD-MTX with IT- Do PET CT after end of 2^nd cycle
• Maintenance- m1 and m2- Given only if CNS positive/ Burkitt lymphoma

COP

• Inj. Vincristine- 1mg/m2- IV Bolus on Day 1
• Inj. Cyclophosphamide- 300mg/m2- as infusion over 15min on day 1
• Tab. Prednisolone- 60mg/m2- in two divided doses- PO- Day 1 to day 7
• IT- Methotrexate and hydrocortisone- on day 1

(Consider 2^nd course of COP, if child is too sick to receive R-COPADM)

R-COPADM (Started on day 8)

• Inj. Rituximab- 375mg/m2 over 4 hrs- on Day 1
• Inj. Vincristine- 2mg/m2 (max dose 2mg)- as IV bolus on day 1
• Tab. Prednisolone- 60mg/m2- in two divided doses- PO- Day 1 to day 5- then taper over 3 days
• Inj. Methotrexate- 3gm/m2- in 500ml/m2D5%- IV- over 3 hrs on day 1
• Inj. Folinic acid- 15mg/m2- 6 hrly for 12 doses- Start at 24 hrs from start of methotrexate infusion
• Cyclophosphamide- 250mg/m2- as infusion over 15min- BD- for 3 days- Total of 6 doses (On days 2, 3, and 4). Hydration- 3000ml/m2- to be continued up to 12 hrs after last cyclophosphamide infusion
• Inj. Doxorubicin- 60mg/m2 over 1 hr- on Day 2
• IT- Methotrexate and hydrocortisone- on 2 days- Day 2 and Day 6 

Start 2^nd course of R-COPADM once ANC is >1000/cmm and platelet count is >1lac/cmm (Generally Day 21)

R-CYM

• Inj. Rituximab- 375mg/m2 over 4 hrs- on Day 1
• Inj. Methotrexate- 3gm/m2- in 500ml/m2D5%- IV- over 3 hrs on day 1
• Inj. Folinic acid- 15mg/m2- 6 hrly for 12 doses- Start at 24 hrs from start of methotrexate infusion
• Inj. Cytarabine- 100mg/m2- in 1000ml/m2 D5%- over 24 hrs from Day 2 to Day 6 (For 5 days)
• IT- Methotrexate and Hydrocortisone on Day 2
• IT- Cytarabine and Hydrocortisone on Day 7

R-CYVE with HD-MTX

• Inj. Rituximab- 375mg/m2 over 4 hrs- on Day 1
• IT- Hydrocortisone and methotrexate on Day 1
• Inj. Cytarabine- 50mg/m2- continuous infusion over 12 hours in D5%- Start at 8pm and finish at 8am- Day 1 to Day 5
• Inj. Cytarabine- 3gm/m2- in 375ml/m2 D5% - IV over 3 hrs- Started at end of 12 hrs of cytosine infusion (start at 8am and finish at 11am)- From day 2 to day 5 (For 4 days)
• Give steroid eye drops- QID
• Inj. Etoposide- 200mg/m2 in 500ml/m2- DNS over 2 hrs- From Day 2 to Day 5 (For 4 days)-Start 3 hrs after end of HD-Cytarabine, i.e. at 2pm.
• On Day 18 (If ANC is >1000/cmm and platelet count is >1lac/cmm)
  • HD MTX- along with Triple IT- Inj. Methotrexate- 8gm/m2- in 500ml/m2D5%- IV- over 4 hrs. Then Inj. Folinic acid- 15mg/m2- 6 hrly for 12 doses- Start at 24 hrs from start of methotrexate infusion
  • If there is CNS involvement- Inj. Methotrexate- 8gm/m2- in 500ml/m2D5%- IV- over 24 hrs. Then Inj. Folinic acid- 15mg/m2- 6 hrly for 12 doses- Start at 36 hrs from start of methotrexate infusion

Start 2^nd course of R-CYVE once ANC is >1000/cmm and platelet count is >1lac/cmm

Maintenance- m1 (Start once ANC is >1000/cmm and platelet count is >1lac/cmm)

• Inj. Vincristine- 2mg/m2 (max dose 2mg)- as IV bolus on day 1
• Tab. Prednisolone- 60mg/m2- in two divided doses- PO- Day 1 to day 5- then taper over 3 days
• Inj. Methotrexate- 8gm/m2- in 500ml/m2D5%- IV- over 3 hrs on day 1
• Inj. Folinic acid- 15mg/m2- 6 hrly for 12 doses- Start at 24 hrs from start of methotrexate infusion

(If there is CNS involvement- Inj. Methotrexate- 8gm/m2- in 500ml/m2D5%- IV- over 24 hrs. Then Inj. Folinic acid- 15mg/m2- 6 hrly for 12 doses- Start at 36 hrs from start of methotrexate infusion)

• Cyclophosphamide- 500mg/m2- as infusion over 30min- for 2 days- (On days 2 and 4). Hydration- 3000ml/m2- to be continued up to 12 hrs after last cyclophosphamide infusion
• Inj. Doxorubicin- 60mg/m2 over 1 hr- on Day 2
• Triple IT- on Day 2 

Maintenance- m2 (Started on day 28 of course m1)

• Inj. Cytarabine- 50mg/m2- SC- BD- Day 1 to Day 5
• Inj. Etoposide- 150mg/m2- IV infusion over 90min- OD- From Day 1 to Day 3.

Composite lymphoma

• Occurrence of two different and well delineated varieties of lymphoma occurring in a single anatomic site or mass

Discordant lymphoma

• Occurrence of two different types of lymphoma at separate anatomic sites
• Examples
  • SLL transforming to DLBLL
  • Mantle cell lymphoma to blastic transformation
  • Mycosis fungoides to DLBLL
  • Classic Hodgkin withDLBCL/ Peripheral T cell lymphoma

Recent advances:

Antivirals as primary treatment for Hepatitis C virus–associated indolent Non-Hodgkin lymphomas: the BART study 

In the present study patients with hepatitis C virus (HCV)–associated indolent lymphomas were treated with genotype-appropriate direct-acting antivirals (17 ledipasvir/sofosbuvir, eight sofosbuvir plus ribavirin, and 15 sofosbuvir/velpatasvir). All patients achieved sustained virologic response. Overall response rate of lymphoma was 45%. 

https://doi.org/10.1200/JCO.22.00668

High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: 

In 2004, the European Mantle Cell Lymphoma Network initiated this trial. First arm patients received alternate R-CHOP/R-DHAP induction followed by high-dose cytarabine-containing myeloablative radiochemotherapy conditioning and autologous peripheral blood stem-cell transplantation. Other arm patients received R-CHOP with standard myeloablative radiochemotherapy and autologous stem-cell transplantation. After a median follow-up of 10.6 years, the time to treatment failure was still significantly improved in the R-DHAP versus R-CHOP arms (medians 8.4 v 3.9 years). 

https://doi.org/10.1200/JCO.22.01780

Lenalidomide maintenance following ASCT in chemo-resistant or high-risk NHL

In this phase I/II study, 59 patients with high-risk relapsed non-Hodgkin lymphoma received BEAM chemotherapy and ASCT followed by 12 months of maintenance lenalidomide. The maximum tolerated dose was 15 mg, but cytopenias led to a reduced dose of 10 mg. Only 27% of patients completed the full 12 cycles of lenalidomide maintenance, with the most common reason for discontinuation being adverse events, primarily haematologic. Two-year progression-free survival (PFS) and overall survival (OS) rates varied across patient groups, but overall, the results did not support the use of lenalidomide maintenance in this setting.

https://doi.org/10.1111/bjh.18821

Mosunetuzumab in Relapsed/Refractory Indolent and Aggressive B-Cell Non-Hodgkin Lymphomas

Mosunetuzumab is a CD20xCD3 T-cell–engaging bispecific antibody. In a phase I/II study of mosunetuzumab in relapsed/refractory indolent (iNHL) and aggressive (aNHL) B-cell non-Hodgkin lymphoma, updated analysis after a median follow-up of 3.5 years showed promising outcomes. Among iNHL patients, 65.7% achieved a complete or partial response, with a median duration of response (DoR) of 23.2 months in all responders and not reached in complete responders. In aNHL, 36.4% responded with a median DoR of 7.8 months. Complete responders to mosunetuzumabshowed no relapses beyond 26 months. Retreatments in progressing complete responders resulted in high objective response rates (83.3%) and second complete responses in 58.3% of cases, demonstrating durable remissions with this fixed-duration, outpatient treatment.

https://doi.org/10.1200/JCO.23.023

Automated Response Assessment in 18F-Fluorodeoxyglucose–Avid Non-Hodgkin Lymphoma With Deep Learning on Positron Emission Tomography

A deep learning-based algorithm for assessing treatment response in 18F-fluorodeoxyglucose–avid lymphomas was tested across multiple trials and demonstrated high agreement with radiologic assessments and superior prognostic accuracy. The algorithm reduced radiologist review time to a median of 1.38 minutes per assessment while maintaining performance comparable to expert evaluations. These findings suggest the algorithm can enhance workflow efficiency in cancer imaging without compromising accuracy.

https://doi.org/10.1200/JCO.23.0197