Australian Doctor 14th July Issue 14JULY2023 issue | Page 41

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Ibrutinib also has an antiplatelet effect that causes easy bruising but usually not significant bleeding . 39 The bleeding risk is exacerbated if there is concurrent antiplatelet or anticoagulation therapy , a common scenario given the older age of many patients with CLL and the increased incidence of AF . NOACs are preferred in this setting over warfarin and consultation with the treating haematologist is recommended around the time of procedures or major surgery .

Newer Bruton ’ s tyrosine kinase inhibitors include acalabrutinib and zanubrutinib . These may achieve equivalent clinical responses to ibrutinib without the risk of toxicities such as cardiac arrhythmias and impaired platelet function . More potent agents such as pirtobrutinib are in clinical trials .

PRO-APOPTOTIC AGENTS Venetoclax impairs the ability of cancer cells to escape natural cell death ( apoptosis ), one of the hallmarks of malignancy . 40 It specifically targets BCL2 , a member of a family of proteins that controls apoptosis . Venetoclax has significant activity in CLL and is approved for treatment in combination with the antibody obinutuzumab in a subset of older patients . The main toxicities

1 . Which THREE statements regarding the adaptive immune system are correct ? a Lymphocytes provide a rapid and sustained defence against pathogens . b B lymphocytes are crucial in the co-ordination of the immune response and control of intracellular pathogens . c Errors in the adaptive immune system lead to abnormal proliferation of lymphocyte clones . d Natural killer cells trigger cytokine release and directly kill virus infected and tumour cells .

2 . Which TWO are well established significant risk factors implicated in the development of lymphoma ? a Immunosuppressed states . b Exposure to ionising radiation . c Epstein-Barr virus . d Cigarette smoking .

3 . Which ONE investigation is , ideally , the minimum required for the diagnosis of lymphoma ? a Fine needle aspiration biopsy of lymph node or tissue . b Positive PET scan . c Core biopsy of lymph node or tissue . d Elevated lymphocyte count with circulating lymphoma cells . are suppression of blood counts , and tumour lysis syndrome because of its efficacy and the rapid breakdown of cancer cells . A strategy to avoid tumour lysis syndrome is to start venetoclax at a low dose with gradual ramping up to the optimal dose while closely monitoring for signs and markers of tumour lysis syndrome .

Radiotherapy

Lymphoma is generally extremely responsive to radiation treatment , which was first used prior to the development of chemotherapy , and it remains the cornerstone of treating early-stage indolent lymphomas . There has been an evolution in radiotherapy technology and strategy over decades to specifically target lymphoma lesions while sparing normal tissue , and thereby minimise toxicity . 41

Access and cost

The rapid development of new and often costly drugs has raised concerns about equitable access to these therapies . 42 There can be a lag between the public reporting of early phase trials , approval by the TGA and eventual funding through the PBS ( see box 3 ). Enrolment into clinical trials may be appropriate for some patients , allowing them to access these novel therapies .

LONG-TERM FOLLOW-UP

THE improvement in the treatment of lymphoma means there is an increasing number of patients

4 . Which THREE statements regarding the investigation of lymphoma are correct ? a A normal FBC excludes lymphoma . b Lactate dehydrogenase may be elevated but is non-specific . c Bone marrow biopsy is not routinely required in many cases . d CT or PET scan may be used for staging at diagnosis and can guide site of biopsy .

5 . Which TWO statements regarding lymphoma are correct ? a Advanced cases affect lymph nodes and organs above and below the diaphragm . b Hodgkin ’ s lymphoma comprises about 70 % of cases of lymphoma . c T-cell non-Hodgkin ’ s lymphomas have better outcomes than their B-cell counterparts . d Many types of B-cell non-Hodgkin ’ s lymphoma are considered curable with a defined course of treatment .

Box 3 . Availability of new drugs

• All medicines for human use must be registered with the TGA ; this process requires a sponsor ( usually the manufacturer ), and evaluation of safety and efficacy .

• TGA approval allows the use of the medicine but does not subsidise the cost of therapy , which can be substantial for novel cancer agents .

• The PBS subsidises the cost of medicines .

• Approval by the PBAC after assessment of drug cost and efficacy is required prior to listing on the PBS .

who have been cured of their malignancy , or who are surviving for many years with ongoing treatment . Although survivorship clinics are being set up in many cancer services for long-term follow-up , GPs remain the main source of primary care for these patients . 43 The monitoring of patients following chemotherapy includes both surveying for relapse of the original disease , as well as monitoring for secondary primary malignancies , which are increased in people previously treated with chemotherapy and / or radiotherapy . Treatment can impair fertility but the effect may vary greatly depending on the specific regimens and drug doses ; specialist review at initiation of therapy and longer-term follow-up

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6 . Which THREE statements regarding the management of lymphoma are correct ? a The patient ’ s age , comorbidities and preferences will guide therapy . b Team-based care is crucial for achieving the best outcomes for patients . c Cytogenetics can define certain lymphoma subtypes and provide prognostic information . d Indolent lymphomas require urgent treatment .

7 . Which THREE are the most common side effects of chemotherapy ? a Diarrhoea . b Nausea and vomiting . c Hair loss . d Suppression of immune system .

8 . Which THREE statements regarding the treatment of lymphoma are correct ? a Checkpoint inhibitors are effective in melanoma , lung cancer and non-Hodgkin ’ s lymphoma . b Monoclonal antibodies induce antibody-dependent

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• Each article has been allocated one hour by the RACGP and ACRRM .

• RACGP points are uploaded every six weeks and ACRRM points quarterly . is warranted . Individualised assessment of other potential late effects , including cardiac disease , endocrine issues ( for example , thyroid disorders and diabetes ), and psychological wellbeing is vital .

Despite the advances in the treatment of lymphoma , not all patients are cured of their disease . The timely involvement of palliative care services can help manage symptoms and distress at the end of life . 44

LYMPHOMA

CASE STUDIES

Case study one

PETER , a 68-year-old mechanic presents with enlarged axillary and inguinal lymph nodes , and a 5kg weight loss . His PET scan shows enlarged and metabolically active lymph nodes in multiple regions above and below the diaphragm : axilla , mediastinum , abdomen and inguinal nodes .

Blood tests reveal a mild anaemia and a raised LDH of 476U / L ( normal 120-250 ). He undergoes an ultrasound guided core biopsy of an axillary node that confirms a DLBCL . Further testing with immunohistochemistry and cytogenetics confirms a ‘ double-hit ’ pattern portending an aggressive course .

Peter starts treatment with R-CHOP chemotherapy . He requires hospital admission and antibiotics after cycle two for fevers , but no source of infection is identified . After cycle four he is again admitted with shortness of breath , and a PET scan shows progressive disease and a new right pleural effusion . He starts salvage chemotherapy with R-DHAP ( rituximab ,

cell-mediated cytotoxicity . c The two key toxicities of bispecific agents are cytokine release syndrome and nephrotoxicity . d Antibody-drug conjugates improve the potency of immunotherapy .

9 . Which THREE statements regarding CAR T-cell therapy are correct ? a Patients may require bridging therapy before starting CAR T-cell therapy . b CAR T-cell therapy uses T-cells engineered with the gene to express a fragment of a virus . c Complications can include low blood counts , infection and long-term need for immunoglobulin replacement . d There are specific eligibility criteria for the use of CAR T-cell therapy .

10 . Which THREE statements regarding the treatment of lymphoma are correct ? a Haemopoietic stem cell transplantation may be autologous or allogeneic . b Targeted small molecule therapies obviate the need for long-term treatment . c Ibrutinib may trigger AF in a minority of patients . d Cancer cells can escape natural cell death . dexamethasone , high-dose ara-C [ cytarabine ], Platinol [ cisplatin ]) with a plan for stem cell collection and autologous stem cell transplantation .

However , after an initial response , he again develops progressive disease with an enlarging abdominal mass and ascites . A further biopsy confirms DLBCL . He is referred to another centre for consideration of clinical trials or CAR T-cell therapy , where he receives radiotherapy as bridging therapy for the abdominal mass before proceeding to CAR T-cell therapy .

Peter requires social and financial support to relocate closer to his new treatment centre , and psychological support throughout his treatment .

Case study two

Sarah , a 29-year-old human resources manager , presents with a history of itch , night sweats and a feeling of fullness on the right side of her neck . On examination she has palpable right supraclavicular lymphadenopathy . A chest X-ray demonstrates a moderate sized anterior mediastinal mass , and she is referred to her local haematology unit . A PET scan shows uptake in a mediastinal mass , and right axillary and cervical lymphadenopathy with no involvement below the diaphragm . She undergoes an excision biopsy of her right supraclavicular node , which is consistent with classical Hodgkin ’ s lymphoma .

Sarah declines any fertility preservation , and after her case is discussed at the hospital multidisciplinary meeting , she receives four cycles of ABVD chemotherapy . There is a small amount of residual PET scan activity at the mediastinum at the end of treatment . She undergoes radiotherapy to the mediastinum , after discussion of benefits and longterm toxicities , after the completion of chemotherapy .

Sarah presents to the haematology clinic six months after completion of therapy with a hoarse voice and cough . A scan shows recurrent lymphadenopathy , and Hodgkin ’ s lymphoma is confirmed on biopsy . She receives salvage chemotherapy with the ICE ( ifosfamide , carboplatin , etoposide ) regimen and is admitted to hospital during the second cycle because of neutropenic sepsis ; another scan demonstrates progressive disease .

Sarah is subsequently treated with brentuximab vedotin over three months and achieves complete remission . She develops mild-to-moderate peripheral neuropathy of her hands but continues to have adequate residual function . There are ongoing discussions about future treatment plans which may include an autologous stem cell transplant .

CONCLUSION

THE treatment of lymphoma is rapidly changing as a range of novel therapies become available . Patients are surviving longer and can remain on treatment for many years in the community . GPs play a key role in the care of these patients , including recognition of toxicities such as infection , communication with treating specialists about adverse events and clinical response , and long-term follow-up of survivors .

References Available on request from howtotreat @ adg . com . au